Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer (PROSPER)

• ClinicalTrials.gov Identifier: NCT02003924
• Recruitment Status: Active, not recruiting
• First Posted: December 6, 2013
• Results First Posted: July 12, 2018
• Last Update Posted: April 23, 2024
• Sponsor: Pfizer
• Collaborators: Astellas Pharma Inc; Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Nonmetastatic Castration-Resistant Prostate Cancer; Prostate Cancer; Cancer of the Prostate
• Interventions: Drug: Enzalutamide; Drug: Placebo
• Enrollment: 1402

Participant Flow

Recruitment Details	The study was conducted at 254 sites in 32 countries.
Pre-assignment Details	A protocol amendment was implemented to unblind all participants and those who were previously treated with placebo had an opportunity to receive open-label access to enzalutamide at the discretion of the investigator.

Arm/Group Title	Enzalutamide 160 mg	Placebo	Placebo Participants Crossover to Enzalutamide 160 mg
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.	Participants who received placebo in double-blind phase and who agreed to proceed to open-label phase, received 4 capsules of Enzalutamide 40 mg each (total dose of 160 mg per day), orally once daily (up to a maximum of 18.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Period Title: Double-blind Phase
Started	933	468	0
Treated	930	465	0
Completed	478	87	0
Not Completed	455	381	0
Reason Not Completed
Lost to Follow-up	2	1	0
Protocol Violation	1	2	0
Withdrawal Consent to Continue Treatment	71	47	0
Disease Progression	229	247	0
Adverse Event	120	31	0
Randomized But not Treated	3	3	0
Other	29	50	0
Period Title: Open-label Phase
Started	478	0 [1]	87 [2]
Treated	478	0	87
Completed	378	0	70
Not Completed	100	0	17
Reason Not Completed
Lost to Follow-up	0	0	1
Withdrawal Consent to Continue Treatment	9	0	1
Disease Progression	59	0	5
Adverse Event	25	0	10
Other	7	0	0
[1] Participants were offered to switch from double blind placebo to open label Enzalutamide.; [2] Participants previously treated with placebo, switched to receive open label Enzalutamide.
Period Title: Long-term Follow-up Phase
Started	933 [1]	381 [2]	87 [3]
Completed	566	144	80
Not Completed	367	237	7
Reason Not Completed
Death	288	174	4
Lost to Follow-up	8	6	1
Withdrew Consent to Be Followed	66	55	1
Other	5	2	1
[1] Participants followed up after discontinuing study drug in either double blind or open label phase.; [2] Participants were followed up after study drug discontinuation in double blind phase.; [3] Participants were followed up after study drug discontinuation in open label phase.

Baseline Characteristics

Arm/Group Title		Enzalutamide 160 mg	Placebo	Total
Arm/Group Description		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.	Total of all reporting groups
Overall Number of Baseline Participants		933	468	1401
Baseline Analysis Population Description		The intent-to-treat (ITT) population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	933 participants	468 participants	1401 participants
		73.8 (7.83)	72.9 (7.63)	73.5 (7.77)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	933 participants	468 participants	1401 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	933 100.0%	468 100.0%	1401 100.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	933 participants	468 participants	1401 participants
Asian		142 15.2%	88 18.8%	230 16.4%
Black or African American		21 2.3%	10 2.1%	31 2.2%
Native Hawaiian or Other Pacific Islander		3 0.3%	2 0.4%	5 0.4%
White		671 71.9%	320 68.4%	991 70.7%
Multiple		4 0.4%	4 0.9%	8 0.6%
Other		15 1.6%	5 1.1%	20 1.4%
Missing		77 8.3%	39 8.3%	116 8.3%

Outcome Measures

1. Primary Outcome

Title	Metastasis Free Survival (MFS)
Description	MFS:time from randomization to first date of radiographic progression (RP) (by Blinded independent central radiology review [BICR]) at any time or death within 112 days of treatment discontinuation without evidence of RP.RP for bone disease:appearance of 1 or more metastatic lesions on bone scan.RP for soft tissue disease:per Response Evaluation Criteria in Solid Tumors,[RECIST 1.1])-at least a 20 percent (%) increase in the sum of diameters of target lesions,taking as reference the smallest sum on study (includes the baseline sum if smallest on study).Participants who did not have MFS event at the time of analysis data cut-off (28 June 2017) were censored at date of last assessment showing no objective evidence of RP prior to skeletal-related event or two or more consecutive missed tumor assessments. Participants who were randomized but later confirmed to have metastatic disease before randomization were censored on date of randomization. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until radiographic progression at any time, or death within 112 days of treatment discontinuation, whichever occurred first (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Median (95% Confidence Interval); Unit of Measure: months
	36.6 [1]; (33.1 to NA)	14.7; (14.2 to 15.0)

[1]

The upper limit of the 95% CI was not estimable due to the small number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was based on stratified log-rank test by prostate-specific antigen (PSA) doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no). Threshold for significance at 0.05 level.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.292
	Confidence Interval	(2-Sided) 95%; 0.241 to 0.352
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

2. Secondary Outcome

Title	Time to Prostate-Specific Antigen (PSA) Progression
Description	Time to PSA progression was defined as the time from randomization to the date of first PSA value demonstrating progression, which was subsequently confirmed. For participants with PSA decline at Week 17, PSA progression was defined according to Prostate Cancer Working Group 2 (PCWG2) guidelines as the date that a 25% or greater increase and an absolute increase of 2 nanograms per milliliter (ng/mL) above the nadir (or baseline for participants with no PSA decline by Week 17) was documented, which was confirmed by a second consecutive value obtained at least 3 weeks or later. Participants without confirmed PSA progression at the time of analysis were right censored at the date of last PSA assessment before the analysis data cut-off date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until first PSA progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Median (95% Confidence Interval); Unit of Measure: months
	37.2 [1]; (33.1 to NA)	3.9; (3.8 to 4.0)

[1]

The upper limit of the 95% CI was not estimable due to the small number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	To maintain the family-wise 2-sided type I error rate at 0.05, a parallel testing strategy between OS (with allocated type I error rate 0.03) and remaining key secondary endpoints (time to PSA progression and time to first use of new antineoplastic therapy with allocated type I error rate 0.02) was performed. Testing was performed only if the primary endpoint was statistically significant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per IXRS. Threshold for significance at 0.02 level.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.066
	Confidence Interval	(2-Sided) 95%; 0.054 to 0.081
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

3. Secondary Outcome

Title	Time to First Use of New Antineoplastic Therapy
Description	Time to first use of new antineoplastic therapy was defined as the time from randomization to first use of new antineoplastic for prostate cancer. Participants not starting treatment with a new antineoplastic therapy at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until first use of new antineoplastic therapy(until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Median (95% Confidence Interval); Unit of Measure: months
	39.6 [1]; (37.7 to NA)	17.7; (16.2 to 19.7)

[1]

The upper limit of the 95% CI was not estimable due to the small number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	To maintain the family-wise 2-sided type I error rate at 0.05, a parallel testing strategy between OS (with allocated type I error rate 0.03) and remaining key secondary endpoints (time to PSA progression and time to first use of new antineoplastic therapy with allocated type I error rate 0.02) was performed. Testing was performed only if the previous endpoint was statistically significant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per IXRS. Threshold for significance at 0.02 level.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.208
	Confidence Interval	(2-Sided) 95%; 0.168 to 0.258
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as the time (in months) from randomization to death from any cause. For participants who were alive at the time of the analysis data cutoff, OS time was censored at the last date the participant was known to be alive or analysis data cutoff date, whichever was earlier. Participants with no post baseline survival information were censored on the date of randomization. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until death (up to a maximum of 68.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Median (95% Confidence Interval); Unit of Measure: months
	67.0 [1]; (64.0 to NA)	56.3; (54.4 to 63.0)

[1]

Lower limit for 95% CI could not be estimated because there were insufficient number of participants with event.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	To maintain family-wise 2-sided type I error rate at 0.05,parallel testing strategy between OS(with allocated type I error rate 0.03)and remaining key secondary endpoints(time to PSA progression and time to first use of new antineoplastic therapy with allocated type I error rate 0.02)was performed.OS tested at error rate 0.05 when both time to PSA progression and time to first use of new antineoplastic therapy were significant. When either failed to show significance.OS was tested at error 0.03.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0011
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per interactive voice/web recognition system (IXRS).
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.734
	Confidence Interval	(2-Sided) 95%; 0.608 to 0.885
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

5. Secondary Outcome

Title	Time to Pain Progression
Description	Pain was assessed using the score from the Brief Pain Inventory-Short Form (BPI-SF) question 3: "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the last 24 hours." Time to this event was defined as the time from randomization to onset of pain progression, where pain progression was defined as a 2-point or more increase from baseline in the question 3 score. Participants without observed pain progression at the time of analysis were right censored at the date of last pain assessment for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization until onset of pain progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Median (95% Confidence Interval); Unit of Measure: months
	18.5; (17.0 to 22.1)	18.4; (14.8 to 22.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6534
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per IXRS.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.959
	Confidence Interval	(2-Sided) 95%; 0.801 to 1.149
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

6. Secondary Outcome

Title	Time to First Use of Cytotoxic Chemotherapy
Description	Time to first use of cytotoxic chemotherapy was defined as the time from randomization to the first use of cytotoxic chemotherapy for prostate cancer. Participants not starting treatment with a cytotoxic chemotherapy for prostate cancer at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization up to the first use of cytotoxic chemotherapy (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (38.1 to NA)	39.7; (38.9 to 41.3)

[1]

The median and upper limit of the 95% CI was not estimable due to the small number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was based on a stratified log-rank test by PSA doubling time (< 6 months, >= 6 months) and prior or concurrent use of a bone targeting agent (yes, no) as per IXRS.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.378
	Confidence Interval	(2-Sided) 95%; 0.282 to 0.507
	Estimation Comments	HR was based on a Cox regression model (with treatment as the only covariate) stratified by factors defined above, and was relative to placebo with < 1 favoring Enzalutamide.

7. Secondary Outcome

Title	Chemotherapy-Free Disease Specific Survival
Description	Chemotherapy-free disease-specific survival was defined as the time from randomization to first use of cytotoxic chemotherapy for prostate cancer or death due to prostate cancer as assessed by the investigator. Participants not starting treatment with a cytotoxic chemotherapy or not known to have died due to prostate cancer at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization up to first use of cytotoxic chemotherapy for prostate cancer or death due to prostate cancer (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Median (95% Confidence Interval); Unit of Measure: months
	39.6 [1]; (37.7 to NA)	38.9; (30.9 to 41.3)

[1]

The upper limit of the 95% CI was not estimable due to the small number of events.

8. Secondary Outcome

Title	Chemotherapy-Free Survival
Description	Chemotherapy-free survival was defined as the time from randomization to first use of cytotoxic chemotherapy for prostate cancer or death due to any cause. Participants not starting treatment with a cytotoxic chemotherapy or not known to have died at the time of analysis were censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.
Time Frame	From randomization up to first use of cytotoxic chemotherapy for prostate cancer or death due to any cause (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Median (95% Confidence Interval); Unit of Measure: months
	38.1 [1]; (37.7 to NA)	34.0; (30.3 to 39.7)

[1]

The upper limit of the 95% CI was not estimable due to the small number of events.

9. Secondary Outcome

Title	Percentage of Participants With Prostate Specific Antigen (PSA) Response
Description	PSA response was calculated at each visit as a decline from baseline in PSA (ng/mL) to the maximal PSA response with thresholds at 50% and 90%. Additionally, PSA response was assessed as a decline to undetectable levels, where undetectable level was defined as below the limit of quantification of the centrally assessed PSA results (the lower limit of quantification was 0.02 ng/mL). PSA response was confirmed by a second consecutive value at least 3 weeks later.
Time Frame	From randomization until first PSA progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Overall number of participants analyzed' = participants with baseline and at least one post-baseline PSA assessment.

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	933	468
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Decrease from Baseline >= 50%	76.3; (73.5 to 79.0)	2.4; (1.2 to 4.2)
Decrease from Baseline >= 90%	55.9; (52.7 to 59.2)	0.4; (0.1 to 1.5)
Decrease to Undetectable Level	9.6; (7.8 to 11.7)	0; (0 to 0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	Decrease from Baseline >= 50%
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was based on a Cochran-Mantel-Haenszel mean score test stratified by PSA doubling time (<6 months, >= 6 months) and prior concurrent use of a bone targeting agent (yes, no) as per IXRS.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	73.96
	Confidence Interval	(2-Sided) 95%; 70.91 to 77.02
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	Decrease from Baseline >= 90%
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was based on a Cochran-Mantel-Haenszel mean score test stratified by PSA doubling time (<6 months, >= 6 months) and prior concurrent use of a bone targeting agent (yes, no) as per IXRS
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	55.52
	Confidence Interval	(2-Sided) 95%; 52.28 to 58.76
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Enzalutamide 160 mg, Placebo
	Comments	Decrease to Undetectable Level
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was based on a Cochran-Mantel-Haenszel mean score test stratified by PSA doubling time (<6 months, >= 6 months) and prior concurrent use of a bone targeting agent (yes, no) as per IXRS.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Response Rate
	Estimated Value	9.65
	Confidence Interval	(2-Sided) 95%; 7.75 to 11.54
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score
Description	The FACT-P questionnaire is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess prostate-related symptoms. Each item was rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score which ranged from 0 to 156 where higher scores represented better quality of life.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	887 participants	439 participants
		119.5 (17.75)	120.8 (16.73)
Change at Week 17	Number Analyzed	815 participants	403 participants
		-4.0 (14.03)	-3.0 (13.87)
Change at Week 33	Number Analyzed	718 participants	329 participants
		-4.6 (14.82)	-3.5 (13.74)
Change at Week 49	Number Analyzed	621 participants	239 participants
		-3.9 (14.70)	-5.0 (15.71)
Change at Week 65	Number Analyzed	522 participants	183 participants
		-4.0 (15.84)	-5.7 (15.04)
Change at Week 81	Number Analyzed	427 participants	139 participants
		-4.1 (15.01)	-7.5 (16.42)
Change at Week 97	Number Analyzed	354 participants	90 participants
		-4.9 (15.31)	-5.9 (15.80)
Change at Week 113	Number Analyzed	264 participants	68 participants
		-5.5 (16.07)	-5.8 (13.16)
Change at Week 129	Number Analyzed	186 participants	37 participants
		-6.3 (17.33)	-8.1 (13.99)
Change at Week 145	Number Analyzed	109 participants	17 participants
		-5.5 (18.75)	-9.8 (15.47)
Change at Week 161	Number Analyzed	38 participants	6 participants
		-8.9 (19.88)	-7.0 (10.95)
Change at Week 177	Number Analyzed	5 participants	1 participants
		-4.8 (13.19)	-5.0

11. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Mobility Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the mobility questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Number; Unit of Measure: participants
Baseline-No problem in walking	Number Analyzed	884 participants	439 participants
		578	298
Baseline-slight problem in walking	Number Analyzed	884 participants	439 participants
		183	100
Baseline-moderate problem in walking	Number Analyzed	884 participants	439 participants
		100	33
Baseline-severe problem in walking	Number Analyzed	884 participants	439 participants
		21	7
Baseline-unable to walk	Number Analyzed	884 participants	439 participants
		2	1
Week 17-no problem in walking	Number Analyzed	840 participants	419 participants
		526	274
Week 17-slight problem in walking	Number Analyzed	840 participants	419 participants
		190	88
Week 17-moderate problem in walking	Number Analyzed	840 participants	419 participants
		87	50
Week 17-severe problem in walking	Number Analyzed	840 participants	419 participants
		32	6
Week 17-unable to walk	Number Analyzed	840 participants	419 participants
		5	1
Week 33-no problem in walking	Number Analyzed	738 participants	342 participants
		431	223
Week 33-slight problem in walking	Number Analyzed	738 participants	342 participants
		162	85
Week 33-moderate problem in walking	Number Analyzed	738 participants	342 participants
		103	24
Week 33-severe problem in walking	Number Analyzed	738 participants	342 participants
		36	10
Week 33-unable to walk	Number Analyzed	738 participants	342 participants
		6	0
Week 49-no problem in walking	Number Analyzed	635 participants	250 participants
		362	156
Week 49-slight problem in walking	Number Analyzed	635 participants	250 participants
		158	57
Week 49-moderate problem in walking	Number Analyzed	635 participants	250 participants
		86	27
Week 49-severe problem in walking	Number Analyzed	635 participants	250 participants
		25	8
Week 49-unable to walk	Number Analyzed	635 participants	250 participants
		4	2
Week 65-no problem in walking	Number Analyzed	536 participants	193 participants
		319	121
Week 65-slight problem in walking	Number Analyzed	536 participants	193 participants
		109	44
Week 65-moderate problem in walking	Number Analyzed	536 participants	193 participants
		75	22
Week 65-severe problem in walking	Number Analyzed	536 participants	193 participants
		29	6
Week 65-unable to walk	Number Analyzed	536 participants	193 participants
		4	0
Week 81-no problem in walking	Number Analyzed	435 participants	148 participants
		236	88
Week 81-slight problem in walking	Number Analyzed	435 participants	148 participants
		111	39
Week 81-moderate problem in walking	Number Analyzed	435 participants	148 participants
		61	15
Week 81-severe problem in walking	Number Analyzed	435 participants	148 participants
		26	4
Week 81-unable to walk	Number Analyzed	435 participants	148 participants
		1	2
Week 97-no problem in walking	Number Analyzed	365 participants	95 participants
		189	59
Week 97-slight problem in walking	Number Analyzed	365 participants	95 participants
		94	24
Week 97-moderate problem in walking	Number Analyzed	365 participants	95 participants
		54	8
Week 97-severe problem in walking	Number Analyzed	365 participants	95 participants
		22	4
Week 97-unable to walk	Number Analyzed	365 participants	95 participants
		6	0
Week 113-no problem in walking	Number Analyzed	275 participants	73 participants
		140	45
Week 113-slight problem in walking	Number Analyzed	275 participants	73 participants
		76	14
Week 113-moderate problem in walking	Number Analyzed	275 participants	73 participants
		41	11
Week 113-severe problem in walking	Number Analyzed	275 participants	73 participants
		14	2
Week 113-unable to walk	Number Analyzed	275 participants	73 participants
		4	1
Week 129-no problem in walking	Number Analyzed	193 participants	41 participants
		94	26
Week 129-slight problem in walking	Number Analyzed	193 participants	41 participants
		48	9
Week 129-moderate problem in walking	Number Analyzed	193 participants	41 participants
		36	5
Week 129-severe problem in walking	Number Analyzed	193 participants	41 participants
		15	1
Week 129-unable to walk	Number Analyzed	193 participants	41 participants
		0	0
Week 145-no problem in walking	Number Analyzed	116 participants	21 participants
		56	13
Week 145-slight problem in walking	Number Analyzed	116 participants	21 participants
		35	5
Week 145-moderate problem in walking	Number Analyzed	116 participants	21 participants
		18	2
Week 145-severe problem in walking	Number Analyzed	116 participants	21 participants
		7	1
Week 145-unable to walk	Number Analyzed	116 participants	21 participants
		0	0
Week 161-no problem in walking	Number Analyzed	40 participants	8 participants
		22	2
Week 161-slight problem in walking	Number Analyzed	40 participants	8 participants
		7	5
Week 161-moderate problem in walking	Number Analyzed	40 participants	8 participants
		6	1
Week 161-severe problem in walking	Number Analyzed	40 participants	8 participants
		5	0
Week 161-unable to walk	Number Analyzed	40 participants	8 participants
		0	0
Week 177-no problem in walking	Number Analyzed	6 participants	1 participants
		3	0
Week 177-slight problem in walking	Number Analyzed	6 participants	1 participants
		2	1
Week 177-moderate problem in walking	Number Analyzed	6 participants	1 participants
		1	0
Week 177-severe problem in walking	Number Analyzed	6 participants	1 participants
		0	0
Week 177-unable to walk	Number Analyzed	6 participants	1 participants
		0	0

12. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Self-Care Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the self-care questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Number; Unit of Measure: participants
Baseline:no problems washing or dressing	Number Analyzed	884 participants	439 participants
		805	415
Baseline:slight problems washing or dressing	Number Analyzed	884 participants	439 participants
		51	23
Baseline:moderate problems washing or dressing	Number Analyzed	884 participants	439 participants
		22	1
Baseline:severe problems washing or dressing	Number Analyzed	884 participants	439 participants
		2	0
Baseline:unable to wash or dress	Number Analyzed	884 participants	439 participants
		4	0
Week 17:no problems washing or dressing	Number Analyzed	840 participants	419 participants
		752	388
Week 17:slight problems washing or dressing	Number Analyzed	840 participants	419 participants
		60	26
Week 17:moderate problems washing or dressing	Number Analyzed	840 participants	419 participants
		21	5
Week 17:severe problems washing or dressing	Number Analyzed	840 participants	419 participants
		6	0
Week 17:unable to wash or dress	Number Analyzed	840 participants	419 participants
		1	0
Week 33:no problems washing or dressing	Number Analyzed	738 participants	342 participants
		642	310
Week 33:slight problems washing or dressing	Number Analyzed	738 participants	342 participants
		64	20
Week 33:moderate problems washing or dressing	Number Analyzed	738 participants	342 participants
		21	10
Week 33:severe problems washing or dressing	Number Analyzed	738 participants	342 participants
		4	1
Week 33:unable to wash or dress	Number Analyzed	738 participants	342 participants
		7	1
Week 49:no problems washing or dressing	Number Analyzed	635 participants	250 participants
		546	230
Week 49:slight problems washing or dressing	Number Analyzed	635 participants	250 participants
		59	9
Week 49:moderate problems washing or dressing	Number Analyzed	635 participants	250 participants
		23	7
Week 49:severe problems washing or dressing	Number Analyzed	635 participants	250 participants
		3	3
Week 49:unable to wash or dress	Number Analyzed	635 participants	250 participants
		4	1
Week 65:no problems washing or dressing	Number Analyzed	536 participants	193 participants
		453	179
Week 65:slight problems washing or dressing	Number Analyzed	536 participants	193 participants
		57	11
Week 65:moderate problems washing or dressing	Number Analyzed	536 participants	193 participants
		14	3
Week 65:severe problems washing or dressing	Number Analyzed	536 participants	193 participants
		9	0
Week 65:unable to wash or dress	Number Analyzed	536 participants	193 participants
		3	0
Week 81:no problems washing or dressing	Number Analyzed	435 participants	148 participants
		356	132
Week 81:slight problems washing or dressing	Number Analyzed	435 participants	148 participants
		57	11
Week 81:moderate problems washing or dressing	Number Analyzed	435 participants	148 participants
		17	3
Week 81:severe problems washing or dressing	Number Analyzed	435 participants	148 participants
		3	1
Week 81:unable to wash or dress	Number Analyzed	435 participants	148 participants
		2	1
Week 97:no problems washing or dressing	Number Analyzed	365 participants	95 participants
		292	85
Week 97:slight problems washing or dressing	Number Analyzed	365 participants	95 participants
		51	8
Week 97:moderate problems washing or dressing	Number Analyzed	365 participants	95 participants
		16	2
Week 97:severe problems washing or dressing	Number Analyzed	365 participants	95 participants
		1	0
Week 97:unable to wash or dress	Number Analyzed	365 participants	95 participants
		5	0
Week 113:no problems washing or dressing	Number Analyzed	275 participants	73 participants
		214	60
Week 113:slight problems washing or dressing	Number Analyzed	275 participants	73 participants
		46	7
Week 113:moderate problems washing or dressing	Number Analyzed	275 participants	73 participants
		11	5
Week 113:severe problems washing or dressing	Number Analyzed	275 participants	73 participants
		0	0
Week 113:unable to wash or dress	Number Analyzed	275 participants	73 participants
		4	1
Week 129:no problems washing or dressing	Number Analyzed	193 participants	41 participants
		147	35
Week 129:slight problems washing or dressing	Number Analyzed	193 participants	41 participants
		28	5
Week 129:moderate problems washing or dressing	Number Analyzed	193 participants	41 participants
		16	1
Week 129:severe problems washing or dressing	Number Analyzed	193 participants	41 participants
		2	0
Week 129:unable to wash or dress	Number Analyzed	193 participants	41 participants
		0	0
Week 145:no problems washing or dressing	Number Analyzed	116 participants	21 participants
		92	15
Week 145:slight problems washing or dressing	Number Analyzed	116 participants	21 participants
		16	5
Week 145:moderate problems washing or dressing	Number Analyzed	116 participants	21 participants
		6	0
Week 145:severe problems washing or dressing	Number Analyzed	116 participants	21 participants
		2	0
Week 145:unable to wash or dress	Number Analyzed	116 participants	21 participants
		0	1
Week 161:no problems washing or dressing	Number Analyzed	40 participants	8 participants
		33	7
Week 161:slight problems washing or dressing	Number Analyzed	40 participants	8 participants
		3	0
Week 161:moderate problems washing or dressing	Number Analyzed	40 participants	8 participants
		2	1
Week 161:severe problems washing or dressing	Number Analyzed	40 participants	8 participants
		1	0
Week 161:unable to wash or dress	Number Analyzed	40 participants	8 participants
		1	0
Week 177:no problems washing or dressing	Number Analyzed	6 participants	1 participants
		3	1
Week 177:slight problems washing or dressing	Number Analyzed	6 participants	1 participants
		3	0
Week 177:moderate problems washing or dressing	Number Analyzed	6 participants	1 participants
		0	0
Week 177:severe problems washing or dressing	Number Analyzed	6 participants	1 participants
		0	0
Week 171:unable to wash or dress	Number Analyzed	6 participants	1 participants
		0	0

13. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Usual Activities Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the usual activities questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Number; Unit of Measure: participants
Baseline:no problems doing usual activities	Number Analyzed	884 participants	439 participants
		646	356
Baseline:slight problems doing usual activities	Number Analyzed	884 participants	439 participants
		167	64
Baseline:moderate problems	Number Analyzed	884 participants	439 participants
		56	14
Baseline:severe problems	Number Analyzed	884 participants	439 participants
		10	5
Baseline:unable to do usual activities	Number Analyzed	884 participants	439 participants
		5	0
Week 17:no problems doing usual activities	Number Analyzed	840 participants	419 participants
		571	305
Week 17:slight problems doing usual activities	Number Analyzed	840 participants	419 participants
		181	89
Week 17:moderate problems	Number Analyzed	840 participants	419 participants
		60	24
Week 17:severe problems	Number Analyzed	840 participants	419 participants
		21	0
Week 17:unable to do usual activities	Number Analyzed	840 participants	419 participants
		7	1
Week 33:no problems doing usual activities	Number Analyzed	738 participants	342 participants
		474	249
Week 33:slight problems doing usual activities	Number Analyzed	738 participants	342 participants
		170	68
Week 33:moderate problems	Number Analyzed	738 participants	342 participants
		68	18
Week 33:severe problems	Number Analyzed	738 participants	342 participants
		21	7
Week 33:unable to do usual activities	Number Analyzed	738 participants	342 participants
		5	0
Week 49:no problems doing usual activities	Number Analyzed	635 participants	250 participants
		418	185
Week 49:slight problems doing usual activities	Number Analyzed	635 participants	250 participants
		137	43
Week 49:moderate problems	Number Analyzed	635 participants	250 participants
		55	14
Week 49:severe problems	Number Analyzed	635 participants	250 participants
		20	6
Week 49:unable to do usual activities	Number Analyzed	635 participants	250 participants
		5	2
Week 65:no problems doing usual activities	Number Analyzed	536 participants	193 participants
		338	136
Week 65:slight problems doing usual activities	Number Analyzed	536 participants	193 participants
		123	42
Week 65:moderate problems	Number Analyzed	536 participants	193 participants
		60	11
Week 65:severe problems	Number Analyzed	536 participants	193 participants
		5	4
Week 65:unable to do usual activities	Number Analyzed	536 participants	193 participants
		10	0
Week 81:no problems doing usual activities	Number Analyzed	435 participants	148 participants
		267	106
Week 81:slight problems doing usual activities	Number Analyzed	435 participants	148 participants
		105	29
Week 81:moderate problems	Number Analyzed	435 participants	148 participants
		49	7
Week 81:severe problems	Number Analyzed	435 participants	148 participants
		10	3
Week 81:unable to do usual activities	Number Analyzed	435 participants	148 participants
		4	3
Week 97:no problems doing usual activities	Number Analyzed	365 participants	95 participants
		224	69
Week 97:slight problems doing usual activities	Number Analyzed	365 participants	95 participants
		90	16
Week 97:moderate problems	Number Analyzed	365 participants	95 participants
		39	8
Week 97:severe problems	Number Analyzed	365 participants	95 participants
		9	0
Week 97:unable to do usual activities	Number Analyzed	365 participants	95 participants
		3	2
Week 113:no problems doing usual activities	Number Analyzed	275 participants	73 participants
		165	47
Week 113:slight problems doing usual activities	Number Analyzed	275 participants	73 participants
		69	16
Week 113:moderate problems	Number Analyzed	275 participants	73 participants
		33	6
Week 113:severe problems	Number Analyzed	275 participants	73 participants
		5	3
Week 113:unable to do usual activities	Number Analyzed	275 participants	73 participants
		3	1
Week 129: Week :no problems doing usual activities	Number Analyzed	193 participants	41 participants
		108	30
Week 129 :slight problems doing usual activities	Number Analyzed	193 participants	41 participants
		56	8
Week 129:moderate problems	Number Analyzed	193 participants	41 participants
		26	3
Week 129:severe problems	Number Analyzed	193 participants	41 participants
		3	0
Week 129:unable to do usual activities	Number Analyzed	193 participants	41 participants
		0	0
Week 145:no problems doing usual activities	Number Analyzed	116 participants	21 participants
		67	14
Week 145:slight problems doing usual activities	Number Analyzed	116 participants	21 participants
		35	4
Week 145:moderate problems	Number Analyzed	116 participants	21 participants
		11	2
Week 145:severe problems	Number Analyzed	116 participants	21 participants
		3	1
Week 145:unable to do usual activities	Number Analyzed	116 participants	21 participants
		0	0
Week 161:no problems doing usual activities	Number Analyzed	40 participants	8 participants
		23	5
Week 161:slight problems doing usual activities	Number Analyzed	40 participants	8 participants
		9	2
Week 161:moderate problems	Number Analyzed	40 participants	8 participants
		5	1
Week 161:severe problems	Number Analyzed	40 participants	8 participants
		2	0
Week 161:unable to do usual activities	Number Analyzed	40 participants	8 participants
		1	0
Week 177:no problems doing usual activities	Number Analyzed	6 participants	1 participants
		3	0
Week 177:slight problems doing usual activities	Number Analyzed	6 participants	1 participants
		2	1
Week 177:moderate problems	Number Analyzed	6 participants	1 participants
		1	0
Week 177:severe problems	Number Analyzed	6 participants	1 participants
		0	0
Week 177:unable to do usual activities	Number Analyzed	6 participants	1 participants
		0	0

14. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Pain/Discomfort Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the pain/discomfort questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline:no pain or discomfort	Number Analyzed	884 participants	439 participants
		546 61.8%	292 66.5%
Baseline:slight pain or discomfort	Number Analyzed	884 participants	439 participants
		240 27.1%	117 26.7%
Baseline:moderate pain or discomfort	Number Analyzed	884 participants	439 participants
		86 9.7%	25 5.7%
Baseline:severe pain or discomfort	Number Analyzed	884 participants	439 participants
		10 1.1%	4 0.9%
Baseline:extreme pain or discomfort	Number Analyzed	884 participants	439 participants
		2 0.2%	1 0.2%
Week 17:no pain or discomfort	Number Analyzed	840 participants	419 participants
		464 55.2%	248 59.2%
Week 17:slight pain or discomfort	Number Analyzed	840 participants	419 participants
		269 32.0%	128 30.5%
Week 17: moderate pain or discomfort	Number Analyzed	840 participants	419 participants
		92 11.0%	41 9.8%
Week 17:severe pain or discomfort	Number Analyzed	840 participants	419 participants
		13 1.5%	2 0.5%
Week 17:extreme pain or discomfort	Number Analyzed	840 participants	419 participants
		2 0.2%	0 0.0%
Week 33:no pain or discomfort	Number Analyzed	738 participants	342 participants
		405 54.9%	204 59.6%
Week 33:slight pain or discomfort	Number Analyzed	738 participants	342 participants
		237 32.1%	110 32.2%
Week 33:moderate pain or discomfort	Number Analyzed	738 participants	342 participants
		79 10.7%	21 6.1%
Week 33:severe pain or discomfort	Number Analyzed	738 participants	342 participants
		16 2.2%	7 2.0%
Week 33:extreme pain or discomfort	Number Analyzed	738 participants	342 participants
		1 0.1%	0 0.0%
Week 49:no pain or discomfort	Number Analyzed	635 participants	250 participants
		340 53.5%	134 53.6%
Week 49:slight pain or discomfort	Number Analyzed	635 participants	250 participants
		209 32.9%	82 32.8%
Week 49:moderate pain or discomfort	Number Analyzed	635 participants	250 participants
		75 11.8%	32 12.8%
Week 49:severe pain or discomfort	Number Analyzed	635 participants	250 participants
		10 1.6%	1 0.4%
Week 49:extreme pain or discomfort	Number Analyzed	635 participants	250 participants
		1 0.2%	1 0.4%
Week 65:no pain or discomfort	Number Analyzed	536 participants	193 participants
		298 55.6%	102 52.8%
Week 65:slight pain or discomfort	Number Analyzed	536 participants	193 participants
		162 30.2%	72 37.3%
Week 65:moderate pain or discomfort	Number Analyzed	536 participants	193 participants
		61 11.4%	15 7.8%
Week 65:severe pain or discomfort	Number Analyzed	536 participants	193 participants
		11 2.1%	3 1.6%
Week 65:extreme pain or discomfort	Number Analyzed	536 participants	193 participants
		4 0.7%	1 0.5%
Week 81:no pain or discomfort	Number Analyzed	435 participants	148 participants
		231 53.1%	86 58.1%
Week 81:slight pain or discomfort	Number Analyzed	435 participants	148 participants
		133 30.6%	45 30.4%
Week 81:moderate pain or discomfort	Number Analyzed	435 participants	148 participants
		61 14.0%	13 8.8%
Week 81 :severe pain or discomfort	Number Analyzed	435 participants	148 participants
		10 2.3%	2 1.4%
Week 81:extreme pain or discomfort	Number Analyzed	435 participants	148 participants
		0 0.0%	2 1.4%
Week 97:no pain or discomfort	Number Analyzed	365 participants	95 participants
		202 55.3%	58 61.1%
Week 97:slight pain or discomfort	Number Analyzed	365 participants	95 participants
		115 31.5%	28 29.5%
Week 97:moderate pain or discomfort	Number Analyzed	365 participants	95 participants
		43 11.8%	7 7.4%
Week 97:severe pain or discomfort	Number Analyzed	365 participants	95 participants
		5 1.4%	2 2.1%
Week 97:extreme pain or discomfort	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113:no pain or discomfort	Number Analyzed	275 participants	73 participants
		152 55.3%	47 64.4%
Week 113:slight pain or discomfort	Number Analyzed	275 participants	73 participants
		80 29.1%	19 26.0%
Week 113:moderate pain or discomfort	Number Analyzed	275 participants	73 participants
		37 13.5%	5 6.8%
Week 113:severe pain or discomfort	Number Analyzed	275 participants	73 participants
		6 2.2%	2 2.7%
Week 113:extreme pain or discomfort	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129:no pain or discomfort	Number Analyzed	193 participants	41 participants
		108 56.0%	27 65.9%
Week 129:slight pain or discomfort	Number Analyzed	193 participants	41 participants
		55 28.5%	11 26.8%
Week 129:moderate pain or discomfort	Number Analyzed	193 participants	41 participants
		28 14.5%	3 7.3%
Week 129:severe pain or discomfort	Number Analyzed	193 participants	41 participants
		2 1.0%	0 0.0%
Week 129:extreme pain or discomfort	Number Analyzed	193 participants	41 participants
		0 0.0%	0 0.0%
Week 145:no pain or discomfort	Number Analyzed	116 participants	21 participants
		62 53.4%	12 57.1%
Week 145:slight pain or discomfort	Number Analyzed	116 participants	21 participants
		38 32.8%	8 38.1%
Week 145:moderate pain or discomfort	Number Analyzed	116 participants	21 participants
		15 12.9%	1 4.8%
Week 145:severe pain or discomfort	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145:extreme pain or discomfort	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161:no pain or discomfort	Number Analyzed	40 participants	8 participants
		24 60.0%	2 25.0%
Week 161:slight pain or discomfort	Number Analyzed	40 participants	8 participants
		8 20.0%	5 62.5%
Week 161:moderate pain or discomfort	Number Analyzed	40 participants	8 participants
		5 12.5%	1 12.5%
Week 161:severe pain or discomfort	Number Analyzed	40 participants	8 participants
		3 7.5%	0 0.0%
Week 161:extreme pain or discomfort	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177:no pain or discomfort	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177:slight pain or discomfort	Number Analyzed	6 participants	1 participants
		1 16.7%	1 100.0%
Week 177:moderate pain or discomfort	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177:severe pain or discomfort	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177:extreme pain or discomfort	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

15. Secondary Outcome

Title	Number of Participants With European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Anxiety/ Depression Domain Score
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the anxiety/depression questionnaire are reported.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline:not anxious or depressed	Number Analyzed	884 participants	439 participants
		595 67.3%	310 70.6%
Baseline:slightly anxious or depressed	Number Analyzed	884 participants	439 participants
		231 26.1%	100 22.8%
Baseline:moderately anxious or depressed	Number Analyzed	884 participants	439 participants
		51 5.8%	24 5.5%
Baseline:severely anxious or depressed	Number Analyzed	884 participants	439 participants
		6 0.7%	5 1.1%
Baseline:extremely anxious or depressed	Number Analyzed	884 participants	439 participants
		1 0.1%	0 0.0%
Week 17:not anxious or depressed	Number Analyzed	840 participants	419 participants
		517 61.5%	265 63.2%
Week 17:slightly anxious or depressed	Number Analyzed	840 participants	419 participants
		251 29.9%	119 28.4%
Week 17:moderately anxious or depressed	Number Analyzed	840 participants	419 participants
		62 7.4%	31 7.4%
Week 17:severely anxious or depressed	Number Analyzed	840 participants	419 participants
		7 0.8%	4 1.0%
Week 17:extremely anxious or depressed	Number Analyzed	840 participants	419 participants
		3 0.4%	0 0.0%
Week 33:not anxious or depressed	Number Analyzed	738 participants	342 participants
		458 62.1%	223 65.2%
Week 33:slightly anxious or depressed	Number Analyzed	738 participants	342 participants
		208 28.2%	89 26.0%
Week 33:moderately anxious or depressed	Number Analyzed	738 participants	342 participants
		61 8.3%	23 6.7%
Week 33:severely anxious or depressed	Number Analyzed	738 participants	342 participants
		9 1.2%	5 1.5%
Week 33:extremely anxious or depressed	Number Analyzed	738 participants	342 participants
		2 0.3%	2 0.6%
Week 49:not anxious or depressed	Number Analyzed	635 participants	250 participants
		410 64.6%	155 62.0%
Week 49:slightly anxious or depressed	Number Analyzed	635 participants	250 participants
		172 27.1%	72 28.8%
Week 49:moderately anxious or depressed	Number Analyzed	635 participants	250 participants
		41 6.5%	20 8.0%
Week 49:severely anxious or depressed	Number Analyzed	635 participants	250 participants
		8 1.3%	2 0.8%
Week 49:extremely anxious or depressed	Number Analyzed	635 participants	250 participants
		4 0.6%	1 0.4%
Week 65:not anxious or depressed	Number Analyzed	536 participants	193 participants
		336 62.7%	128 66.3%
Week 65:slightly anxious or depressed	Number Analyzed	536 participants	193 participants
		149 27.8%	56 29.0%
Week 65:moderately anxious or depressed	Number Analyzed	536 participants	193 participants
		43 8.0%	8 4.1%
Week 65:severely anxious or depressed	Number Analyzed	536 participants	193 participants
		8 1.5%	1 0.5%
Week 65:extremely anxious or depressed	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81:not anxious or depressed	Number Analyzed	435 participants	148 participants
		288 66.2%	86 58.1%
Week 81:slightly anxious or depressed	Number Analyzed	435 participants	148 participants
		106 24.4%	48 32.4%
Week 81:moderately anxious or depressed	Number Analyzed	435 participants	148 participants
		34 7.8%	9 6.1%
Week 81:severely anxious or depressed	Number Analyzed	435 participants	148 participants
		7 1.6%	3 2.0%
Week 81:extremely anxious or depressed	Number Analyzed	435 participants	148 participants
		0 0.0%	2 1.4%
Week 97:not anxious or depressed	Number Analyzed	365 participants	95 participants
		220 60.3%	61 64.2%
Week 97:slightly anxious or depressed	Number Analyzed	365 participants	95 participants
		114 31.2%	27 28.4%
Week 97:moderately anxious or depressed	Number Analyzed	365 participants	95 participants
		26 7.1%	6 6.3%
Week 97:severely anxious or depressed	Number Analyzed	365 participants	95 participants
		4 1.1%	0 0.0%
Week 97:extremely anxious or depressed	Number Analyzed	365 participants	95 participants
		1 0.3%	1 1.1%
Week 113:not anxious or depressed	Number Analyzed	275 participants	73 participants
		167 60.7%	43 58.9%
Week 113:slightly anxious or depressed	Number Analyzed	275 participants	73 participants
		87 31.6%	27 37.0%
Week 113:moderately anxious or depressed	Number Analyzed	275 participants	73 participants
		18 6.5%	3 4.1%
Week 113:severely anxious or depressed	Number Analyzed	275 participants	73 participants
		3 1.1%	0 0.0%
Week 113:extremely anxious or depressed	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129:not anxious or depressed	Number Analyzed	193 participants	41 participants
		121 62.7%	28 68.3%
Week 129:slightly anxious or depressed	Number Analyzed	193 participants	41 participants
		51 26.4%	10 24.4%
Week 129:moderately anxious or depressed	Number Analyzed	193 participants	41 participants
		18 9.3%	2 4.9%
Week 129:severely anxious or depressed	Number Analyzed	193 participants	41 participants
		2 1.0%	1 2.4%
Week 129:extremely anxious or depressed	Number Analyzed	193 participants	41 participants
		1 0.5%	0 0.0%
Week 145:not anxious or depressed	Number Analyzed	116 participants	21 participants
		73 62.9%	12 57.1%
Week 145:slightly anxious or depressed	Number Analyzed	116 participants	21 participants
		30 25.9%	8 38.1%
Week 145:moderately anxious or depressed	Number Analyzed	116 participants	21 participants
		10 8.6%	1 4.8%
Week 145:severely anxious or depressed	Number Analyzed	116 participants	21 participants
		2 1.7%	0 0.0%
Week 145:extremely anxious or depressed	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 161:not anxious or depressed	Number Analyzed	40 participants	8 participants
		23 57.5%	3 37.5%
Week 161:slightly anxious or depressed	Number Analyzed	40 participants	8 participants
		16 40.0%	4 50.0%
Week 161:moderately anxious or depressed	Number Analyzed	40 participants	8 participants
		0 0.0%	1 12.5%
Week 161:severely anxious or depressed	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161:extremely anxious or depressed	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 177:not anxious or depressed	Number Analyzed	933 participants	1 participants
		2 0.2%	1 100.0%
Week 177:slightly anxious or depressed	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177:moderately anxious or depressed	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177:severely anxious or depressed	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177:extremely anxious or depressed	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

16. Secondary Outcome

Title	European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Status Visual Analog Score (VAS)
Description	EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified timepoints.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	884 participants	439 participants
		76.2 (16.92)	77.5 (15.97)
Week 17	Number Analyzed	840 participants	419 participants
		74.7 (17.19)	74.9 (16.79)
Week 33	Number Analyzed	738 participants	342 participants
		74.6 (16.69)	74.0 (17.51)
Week 49	Number Analyzed	635 participants	250 participants
		74.7 (18.02)	73.7 (18.28)
Week 65	Number Analyzed	536 participants	193 participants
		74.5 (17.79)	73.0 (17.11)
Week 81	Number Analyzed	435 participants	148 participants
		75.5 (17.06)	73.3 (16.82)
Week 97	Number Analyzed	365 participants	95 participants
		74.4 (17.39)	75.2 (17.88)
Week 113	Number Analyzed	275 participants	73 participants
		73.6 (18.05)	74.7 (15.06)
Week 129	Number Analyzed	193 participants	41 participants
		72.8 (18.25)	77.1 (12.83)
Week 145	Number Analyzed	116 participants	21 participants
		75.3 (17.02)	74.2 (18.13)
Week 161	Number Analyzed	40 participants	8 participants
		74.6 (21.28)	73.8 (17.60)
Week 177	Number Analyzed	6 participants	1 participants
		74.5 (19.31)	69.0

17. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 31
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 31 are reported. Question 31 was following: "Have you had to urinate frequently during the day?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		285 32.2%	162 36.9%
Baseline: a little	Number Analyzed	884 participants	439 participants
		348 39.4%	160 36.4%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		207 23.4%	92 21.0%
Baseline: very much	Number Analyzed	884 participants	439 participants
		44 5.0%	25 5.7%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		275 32.8%	134 32.0%
Week 17: a little	Number Analyzed	839 participants	419 participants
		324 38.6%	168 40.1%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		194 23.1%	90 21.5%
Week 17: very much	Number Analyzed	839 participants	419 participants
		46 5.5%	27 6.4%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		236 32.0%	105 30.8%
Week 33: a little	Number Analyzed	737 participants	341 participants
		285 38.7%	145 42.5%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		176 23.9%	70 20.5%
Week 33: very much	Number Analyzed	737 participants	341 participants
		40 5.4%	21 6.2%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		200 31.5%	82 32.8%
Week 49: a little	Number Analyzed	635 participants	250 participants
		260 40.9%	92 36.8%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		148 23.3%	67 26.8%
Week 49: very much	Number Analyzed	635 participants	250 participants
		27 4.3%	9 3.6%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		172 32.1%	54 28.0%
Week 65: a little	Number Analyzed	536 participants	193 participants
		209 39.0%	79 40.9%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		125 23.3%	48 24.9%
Week 65: very much	Number Analyzed	536 participants	193 participants
		30 5.6%	12 6.2%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		141 32.5%	46 31.1%
Week 81: a little	Number Analyzed	434 participants	148 participants
		181 41.7%	60 40.5%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		92 21.2%	31 20.9%
Week 81: very much	Number Analyzed	434 participants	148 participants
		20 4.6%	11 7.4%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		118 32.3%	33 34.7%
Week 97: a little	Number Analyzed	365 participants	95 participants
		146 40.0%	40 42.1%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		80 21.9%	19 20.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		21 5.8%	3 3.2%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		101 36.7%	17 23.3%
Week 113: a little	Number Analyzed	275 participants	73 participants
		112 40.7%	40 54.8%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		46 16.7%	14 19.2%
Week 113: very much	Number Analyzed	275 participants	73 participants
		16 5.8%	2 2.7%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		70 36.5%	11 26.8%
Week 129: a little	Number Analyzed	192 participants	41 participants
		79 41.1%	16 39.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		39 20.3%	10 24.4%
Week 129: very much	Number Analyzed	192 participants	41 participants
		4 2.1%	4 9.8%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		42 36.2%	2 9.5%
Week 145: a little	Number Analyzed	116 participants	21 participants
		51 44.0%	14 66.7%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		20 17.2%	4 19.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		3 2.6%	1 4.8%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		9 22.5%	2 25.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		20 50.0%	4 50.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		7 17.5%	1 12.5%
Week 161: very much	Number Analyzed	40 participants	8 participants
		4 10.0%	1 12.5%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		4 66.7%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

18. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 32
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 32 are reported. Question 32 was following: "Have you had to urinate frequently at night?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		193 21.8%	108 24.6%
Baseline: a little	Number Analyzed	884 participants	439 participants
		423 47.9%	195 44.4%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		200 22.6%	103 23.5%
Baseline: very much	Number Analyzed	884 participants	439 participants
		68 7.7%	33 7.5%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		194 23.1%	88 21.0%
Week 17: a little	Number Analyzed	839 participants	419 participants
		407 48.5%	199 47.5%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		184 21.9%	98 23.4%
Week 17: very much	Number Analyzed	839 participants	419 participants
		54 6.4%	34 8.1%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		173 23.5%	83 24.3%
Week 33: a little	Number Analyzed	737 participants	341 participants
		351 47.6%	161 47.2%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		169 22.9%	69 20.2%
Week 33: very much	Number Analyzed	737 participants	341 participants
		44 6.0%	28 8.2%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		148 23.3%	59 23.6%
Week 49: a little	Number Analyzed	635 participants	250 participants
		313 49.3%	116 46.4%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		141 22.2%	59 23.6%
Week 49: very much	Number Analyzed	635 participants	250 participants
		33 5.2%	16 6.4%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		118 22.0%	41 21.2%
Week 65: a little	Number Analyzed	536 participants	193 participants
		266 49.6%	89 46.1%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		111 20.7%	48 24.9%
Week 65: very much	Number Analyzed	536 participants	193 participants
		41 7.6%	15 7.8%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		91 21.0%	38 25.7%
Week 81: a little	Number Analyzed	434 participants	148 participants
		231 53.2%	60 40.5%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		89 20.5%	38 25.7%
Week 81: very much	Number Analyzed	434 participants	148 participants
		23 5.3%	12 8.1%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		88 24.1%	19 20.0%
Week 97: a little	Number Analyzed	365 participants	95 participants
		169 46.3%	53 55.8%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		82 22.5%	19 20.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		26 7.1%	4 4.2%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		67 24.4%	16 21.9%
Week 113: a little	Number Analyzed	275 participants	73 participants
		137 49.8%	32 43.8%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		54 19.6%	23 31.5%
Week 113: very much	Number Analyzed	275 participants	73 participants
		17 6.2%	2 2.7%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		50 26.0%	9 22.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		97 50.5%	18 43.9%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		37 19.3%	10 24.4%
Week 129: very much	Number Analyzed	192 participants	41 participants
		8 4.2%	4 9.8%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		31 26.7%	2 9.5%
Week 145: a little	Number Analyzed	116 participants	21 participants
		59 50.9%	14 66.7%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		24 20.7%	5 23.8%
Week 145: very much	Number Analyzed	116 participants	21 participants
		2 1.7%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		9 22.5%	0 0.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		23 57.5%	7 87.5%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		5 12.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		3 7.5%	1 12.5%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		2 33.3%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

19. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 33
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 33 are reported. Question 33 was following: "When you felt the urge to pass urine, did you have to hurry to get to the toilet?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		406 45.9%	197 44.9%
Baseline: a little	Number Analyzed	884 participants	439 participants
		266 30.1%	147 33.5%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		150 17.0%	70 15.9%
Baseline: very much	Number Analyzed	884 participants	439 participants
		62 7.0%	25 5.7%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		350 41.7%	191 45.6%
Week 17: a little	Number Analyzed	839 participants	419 participants
		297 35.4%	150 35.8%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		127 15.1%	55 13.1%
Week 17: very much	Number Analyzed	839 participants	419 participants
		65 7.7%	23 5.5%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		279 37.9%	147 43.1%
Week 33: a little	Number Analyzed	737 participants	341 participants
		278 37.7%	126 37.0%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		126 17.1%	48 14.1%
Week 33: very much	Number Analyzed	737 participants	341 participants
		54 7.3%	20 5.9%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		272 42.8%	100 40.0%
Week 49: a little	Number Analyzed	635 participants	250 participants
		222 35.0%	95 38.0%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		96 15.1%	38 15.2%
Week 49: very much	Number Analyzed	635 participants	250 participants
		45 7.1%	17 6.8%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		213 39.7%	76 39.4%
Week 65: a little	Number Analyzed	536 participants	193 participants
		213 39.7%	72 37.3%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		71 13.2%	31 16.1%
Week 65: very much	Number Analyzed	536 participants	193 participants
		39 7.3%	14 7.3%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		181 41.7%	63 42.6%
Week 81: a little	Number Analyzed	434 participants	148 participants
		157 36.2%	52 35.1%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		69 15.9%	27 18.2%
Week 81: very much	Number Analyzed	434 participants	148 participants
		27 6.2%	6 4.1%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		146 40.0%	40 42.1%
Week 97: a little	Number Analyzed	365 participants	95 participants
		131 35.9%	40 42.1%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		59 16.2%	12 12.6%
Week 97: very much	Number Analyzed	365 participants	95 participants
		29 7.9%	3 3.2%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		114 41.5%	29 39.7%
Week 113: a little	Number Analyzed	275 participants	73 participants
		106 38.5%	34 46.6%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		40 14.5%	9 12.3%
Week 113: very much	Number Analyzed	275 participants	73 participants
		15 5.5%	1 1.4%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		86 44.8%	10 24.4%
Week 129: a little	Number Analyzed	192 participants	41 participants
		72 37.5%	21 51.2%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		26 13.5%	6 14.6%
Week 129: very much	Number Analyzed	192 participants	41 participants
		8 4.2%	4 9.8%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		51 44.0%	5 23.8%
Week 145: a little	Number Analyzed	116 participants	21 participants
		39 33.6%	12 57.1%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		21 18.1%	4 19.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		5 4.3%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		17 42.5%	0 0.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		19 47.5%	5 62.5%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		3 7.5%	3 37.5%
Week 161: very much	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		1 16.7%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

20. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 34
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 34 are reported. Question 34 was following: "Was it difficult for you to get enough sleep, because you needed to get up frequently at night to urinate?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		479 54.2%	235 53.5%
Baseline: a little	Number Analyzed	884 participants	439 participants
		273 30.9%	146 33.3%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		93 10.5%	40 9.1%
Baseline: very much	Number Analyzed	884 participants	439 participants
		39 4.4%	18 4.1%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		437 52.1%	214 51.1%
Week 17: a little	Number Analyzed	839 participants	419 participants
		295 35.2%	144 34.4%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		75 8.9%	45 10.7%
Week 17: very much	Number Analyzed	839 participants	419 participants
		32 3.8%	16 3.8%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		392 53.2%	180 52.8%
Week 33: a little	Number Analyzed	737 participants	341 participants
		246 33.4%	112 32.8%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		75 10.2%	33 9.7%
Week 33: very much	Number Analyzed	737 participants	341 participants
		24 3.3%	16 4.7%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		340 53.5%	119 47.6%
Week 49: a little	Number Analyzed	635 participants	250 participants
		211 33.2%	94 37.6%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		65 10.2%	28 11.2%
Week 49: very much	Number Analyzed	635 participants	250 participants
		19 3.0%	9 3.6%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		286 53.4%	92 47.7%
Week 65: a little	Number Analyzed	536 participants	193 participants
		183 34.1%	67 34.7%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		47 8.8%	29 15.0%
Week 65: very much	Number Analyzed	536 participants	193 participants
		20 3.7%	5 2.6%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		221 50.9%	70 47.3%
Week 81: a little	Number Analyzed	434 participants	148 participants
		165 38.0%	55 37.2%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		37 8.5%	18 12.2%
Week 81: very much	Number Analyzed	434 participants	148 participants
		11 2.5%	5 3.4%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		185 50.7%	47 49.5%
Week 97: a little	Number Analyzed	365 participants	95 participants
		122 33.4%	33 34.7%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		43 11.8%	14 14.7%
Week 97: very much	Number Analyzed	365 participants	95 participants
		15 4.1%	1 1.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		135 49.1%	31 42.5%
Week 113: a little	Number Analyzed	275 participants	73 participants
		102 37.1%	33 45.2%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		29 10.5%	7 9.6%
Week 113: very much	Number Analyzed	275 participants	73 participants
		9 3.3%	2 2.7%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		103 53.6%	13 31.7%
Week 129: a little	Number Analyzed	192 participants	41 participants
		67 34.9%	23 56.1%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		19 9.9%	4 9.8%
Week 129: very much	Number Analyzed	192 participants	41 participants
		3 1.6%	1 2.4%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		59 50.9%	9 42.9%
Week 145: a little	Number Analyzed	116 participants	21 participants
		44 37.9%	10 47.6%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		11 9.5%	1 4.8%
Week 145: very much	Number Analyzed	116 participants	21 participants
		2 1.7%	1 4.8%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		21 52.5%	2 25.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		16 40.0%	5 62.5%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		3 7.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	1 12.5%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		1 16.7%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

21. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 35
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 35 are reported. Question 35 was following: "Have you had difficulty going out of the house because you needed to be close to a toilet?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		646 73.1%	330 75.2%
Baseline: a little	Number Analyzed	884 participants	439 participants
		177 20.0%	84 19.1%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		45 5.1%	18 4.1%
Baseline: very much	Number Analyzed	884 participants	439 participants
		16 1.8%	7 1.6%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		604 72.0%	295 70.4%
Week 17: a little	Number Analyzed	839 participants	419 participants
		174 20.7%	100 23.9%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		46 5.5%	15 3.6%
Week 17: very much	Number Analyzed	839 participants	419 participants
		15 1.8%	9 2.1%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		501 68.0%	242 71.0%
Week 33: a little	Number Analyzed	737 participants	341 participants
		171 23.2%	74 21.7%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		50 6.8%	20 5.9%
Week 33: very much	Number Analyzed	737 participants	341 participants
		15 2.0%	5 1.5%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		436 68.7%	174 69.6%
Week 49: a little	Number Analyzed	635 participants	250 participants
		153 24.1%	53 21.2%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		38 6.0%	20 8.0%
Week 49: very much	Number Analyzed	635 participants	250 participants
		8 1.3%	3 1.2%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		369 68.8%	132 68.4%
Week 65: a little	Number Analyzed	536 participants	193 participants
		125 23.3%	50 25.9%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		28 5.2%	9 4.7%
Week 65: very much	Number Analyzed	536 participants	193 participants
		14 2.6%	2 1.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		308 71.0%	105 70.9%
Week 81: a little	Number Analyzed	434 participants	148 participants
		94 21.7%	35 23.6%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		23 5.3%	8 5.4%
Week 81: very much	Number Analyzed	434 participants	148 participants
		9 2.1%	0 0.0%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		241 66.0%	67 70.5%
Week 97: a little	Number Analyzed	365 participants	95 participants
		91 24.9%	21 22.1%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		26 7.1%	6 6.3%
Week 97: very much	Number Analyzed	365 participants	95 participants
		7 1.9%	1 1.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		180 65.5%	47 64.4%
Week 113: a little	Number Analyzed	275 participants	73 participants
		70 25.5%	21 28.8%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		18 6.5%	5 6.8%
Week 113: very much	Number Analyzed	275 participants	73 participants
		7 2.5%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		131 68.2%	26 63.4%
Week 129: a little	Number Analyzed	192 participants	41 participants
		48 25.0%	13 31.7%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		8 4.2%	1 2.4%
Week 129: very much	Number Analyzed	192 participants	41 participants
		5 2.6%	1 2.4%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		74 63.8%	13 61.9%
Week 145: a little	Number Analyzed	116 participants	21 participants
		36 31.0%	6 28.6%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		6 5.2%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	2 9.5%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		24 60.0%	4 50.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		13 32.5%	4 50.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		3 7.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		3 50.0%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

22. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 36
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 36 are reported. Question 36 was following: "Have you had any unintentional release (leakage) of urine?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		550 62.2%	283 64.5%
Baseline: a little	Number Analyzed	884 participants	439 participants
		273 30.9%	124 28.2%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		36 4.1%	20 4.6%
Baseline: very much	Number Analyzed	884 participants	439 participants
		25 2.8%	12 2.7%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		511 60.9%	255 60.9%
Week 17: a little	Number Analyzed	839 participants	419 participants
		264 31.5%	126 30.1%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		39 4.6%	27 6.4%
Week 17: very much	Number Analyzed	839 participants	419 participants
		25 3.0%	11 2.6%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		428 58.1%	208 61.0%
Week 33: a little	Number Analyzed	737 participants	341 participants
		246 33.4%	104 30.5%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		34 4.6%	19 5.6%
Week 33: very much	Number Analyzed	737 participants	341 participants
		29 3.9%	10 2.9%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		369 58.1%	146 58.4%
Week 49: a little	Number Analyzed	635 participants	250 participants
		209 32.9%	78 31.2%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		41 6.5%	22 8.8%
Week 49: very much	Number Analyzed	635 participants	250 participants
		16 2.5%	4 1.6%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		307 57.3%	115 59.6%
Week 65: a little	Number Analyzed	536 participants	193 participants
		170 31.7%	66 34.2%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		47 8.8%	8 4.1%
Week 65: very much	Number Analyzed	536 participants	193 participants
		12 2.2%	4 2.1%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		248 57.1%	93 62.8%
Week 81: a little	Number Analyzed	434 participants	148 participants
		158 36.4%	41 27.7%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		23 5.3%	11 7.4%
Week 81: very much	Number Analyzed	434 participants	148 participants
		5 1.2%	3 2.0%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		195 53.4%	55 57.9%
Week 97: a little	Number Analyzed	365 participants	95 participants
		134 36.7%	33 34.7%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		25 6.8%	7 7.4%
Week 97: very much	Number Analyzed	365 participants	95 participants
		11 3.0%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		160 58.2%	42 57.5%
Week 113: a little	Number Analyzed	275 participants	73 participants
		91 33.1%	28 38.4%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		17 6.2%	3 4.1%
Week 113: very much	Number Analyzed	275 participants	73 participants
		7 2.5%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		109 56.8%	22 53.7%
Week 129: a little	Number Analyzed	192 participants	41 participants
		68 35.4%	13 31.7%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		13 6.8%	5 12.2%
Week 129: very much	Number Analyzed	192 participants	41 participants
		2 1.0%	1 2.4%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		58 50.0%	9 42.9%
Week 145: a little	Number Analyzed	116 participants	21 participants
		45 38.8%	11 52.4%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		10 8.6%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		3 2.6%	1 4.8%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		18 45.0%	3 37.5%
Week 161: a little	Number Analyzed	40 participants	8 participants
		21 52.5%	4 50.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		0 0.0%	1 12.5%
Week 161: very much	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		3 50.0%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

23. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 37
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 37 are reported. Question 37 was following: "Did you have pain when you urinated?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		775 87.7%	380 86.6%
Baseline: a little	Number Analyzed	884 participants	439 participants
		92 10.4%	47 10.7%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		10 1.1%	8 1.8%
Baseline: very much	Number Analyzed	884 participants	439 participants
		7 0.8%	4 0.9%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		762 90.8%	351 83.8%
Week 17: a little	Number Analyzed	839 participants	419 participants
		65 7.7%	58 13.8%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		12 1.4%	8 1.9%
Week 17: very much	Number Analyzed	839 participants	419 participants
		0 0.0%	2 0.5%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		662 89.8%	291 85.3%
Week 33: a little	Number Analyzed	737 participants	341 participants
		63 8.5%	39 11.4%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		11 1.5%	8 2.3%
Week 33: very much	Number Analyzed	737 participants	341 participants
		1 0.1%	3 0.9%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		577 90.9%	209 83.6%
Week 49: a little	Number Analyzed	635 participants	250 participants
		49 7.7%	34 13.6%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		6 0.9%	3 1.2%
Week 49: very much	Number Analyzed	635 participants	250 participants
		3 0.5%	4 1.6%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		492 91.8%	161 83.4%
Week 65: a little	Number Analyzed	536 participants	193 participants
		32 6.0%	29 15.0%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		9 1.7%	2 1.0%
Week 65: very much	Number Analyzed	536 participants	193 participants
		3 0.6%	1 0.5%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		389 89.6%	119 80.4%
Week 81: a little	Number Analyzed	434 participants	148 participants
		40 9.2%	27 18.2%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		4 0.9%	2 1.4%
Week 81: very much	Number Analyzed	434 participants	148 participants
		1 0.2%	0 0.0%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		332 91.0%	84 88.4%
Week 97: a little	Number Analyzed	365 participants	95 participants
		28 7.7%	11 11.6%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		4 1.1%	0 0.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		1 0.3%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		247 89.8%	57 78.1%
Week 113: a little	Number Analyzed	275 participants	73 participants
		26 9.5%	13 17.8%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		1 0.4%	3 4.1%
Week 113: very much	Number Analyzed	275 participants	73 participants
		1 0.4%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		173 90.1%	34 82.9%
Week 129: a little	Number Analyzed	192 participants	41 participants
		16 8.3%	7 17.1%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		2 1.0%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		102 87.9%	15 71.4%
Week 145: a little	Number Analyzed	116 participants	21 participants
		14 12.1%	6 28.6%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		36 90.0%	6 75.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		3 7.5%	1 12.5%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	1 12.5%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		6 100.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

24. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 38
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 38 are reported. Question 38 was following: "Has wearing an incontinence aid been a problem for you?". This question was answered by only those participants who wore incontinence aid.
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	144 participants	67 participants
		83 57.6%	37 55.2%
Baseline: a little	Number Analyzed	144 participants	67 participants
		40 27.8%	19 28.4%
Baseline: quite a bit	Number Analyzed	144 participants	67 participants
		15 10.4%	3 4.5%
Baseline: very much	Number Analyzed	144 participants	67 participants
		6 4.2%	8 11.9%
Baseline: not answered	Number Analyzed	144 participants	67 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		77 9.2%	34 8.1%
Week 17: a little	Number Analyzed	839 participants	419 participants
		48 5.7%	21 5.0%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		15 1.8%	7 1.7%
Week 17: very much	Number Analyzed	839 participants	419 participants
		6 0.7%	6 1.4%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		693 82.6%	351 83.8%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		76 10.3%	30 8.8%
Week 33: a little	Number Analyzed	737 participants	341 participants
		47 6.4%	28 8.2%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		16 2.2%	4 1.2%
Week 33: very much	Number Analyzed	737 participants	341 participants
		5 0.7%	4 1.2%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		593 80.5%	275 80.6%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		73 11.5%	18 7.2%
Week 49: a little	Number Analyzed	635 participants	250 participants
		43 6.8%	16 6.4%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		12 1.9%	9 3.6%
Week 49: very much	Number Analyzed	635 participants	250 participants
		4 0.6%	2 0.8%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		503 79.2%	205 82.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		63 11.8%	12 6.2%
Week 65: a little	Number Analyzed	536 participants	193 participants
		40 7.5%	17 8.8%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		9 1.7%	5 2.6%
Week 65: very much	Number Analyzed	536 participants	193 participants
		3 0.6%	1 0.5%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		421 78.5%	158 81.9%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		52 12.0%	15 10.1%
Week 81: a little	Number Analyzed	434 participants	148 participants
		33 7.6%	9 6.1%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		10 2.3%	1 0.7%
Week 81: very much	Number Analyzed	434 participants	148 participants
		3 0.7%	3 2.0%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		336 77.4%	120 81.1%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		50 13.7%	8 8.4%
Week 97: a little	Number Analyzed	365 participants	95 participants
		28 7.7%	8 8.4%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		7 1.9%	2 2.1%
Week 97: very much	Number Analyzed	365 participants	95 participants
		3 0.8%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		277 75.9%	77 81.1%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		31 11.3%	12 16.4%
Week 113: a little	Number Analyzed	275 participants	73 participants
		18 6.5%	7 9.6%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		8 2.9%	2 2.7%
Week 113: very much	Number Analyzed	275 participants	73 participants
		2 0.7%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		216 78.5%	52 71.2%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		27 14.1%	5 12.2%
Week 129: a little	Number Analyzed	192 participants	41 participants
		18 9.4%	5 12.2%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		2 1.0%	1 2.4%
Week 129: very much	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		145 75.5%	30 73.2%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		16 13.8%	2 9.5%
Week 145: a little	Number Analyzed	116 participants	21 participants
		10 8.6%	4 19.0%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		5 4.3%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		85 73.3%	15 71.4%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		10 25.0%	1 12.5%
Week 161: a little	Number Analyzed	40 participants	8 participants
		3 7.5%	2 25.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	1 12.5%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		26 65.0%	4 50.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		2 33.3%	1 100.0%

25. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 39
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 39 are reported. Question 39 was following: "Have your daily activities been limited by your urinary problems?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		666 75.3%	338 77.0%
Baseline: a little	Number Analyzed	884 participants	439 participants
		173 19.6%	80 18.2%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		35 4.0%	11 2.5%
Baseline: very much	Number Analyzed	884 participants	439 participants
		10 1.1%	10 2.3%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		632 75.3%	305 72.8%
Week 17: a little	Number Analyzed	839 participants	419 participants
		160 19.1%	99 23.6%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		36 4.3%	6 1.4%
Week 17: very much	Number Analyzed	839 participants	419 participants
		11 1.3%	9 2.1%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		523 71.0%	242 71.0%
Week 33: a little	Number Analyzed	737 participants	341 participants
		172 23.3%	79 23.2%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		31 4.2%	14 4.1%
Week 33: very much	Number Analyzed	737 participants	341 participants
		11 1.5%	6 1.8%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		444 69.9%	173 69.2%
Week 49: a little	Number Analyzed	635 participants	250 participants
		152 23.9%	58 23.2%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		31 4.9%	18 7.2%
Week 49: very much	Number Analyzed	635 participants	250 participants
		8 1.3%	1 0.4%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		382 71.3%	128 66.3%
Week 65: a little	Number Analyzed	536 participants	193 participants
		124 23.1%	51 26.4%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		20 3.7%	12 6.2%
Week 65: very much	Number Analyzed	536 participants	193 participants
		10 1.9%	2 1.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		310 71.4%	103 69.6%
Week 81: a little	Number Analyzed	434 participants	148 participants
		98 22.6%	35 23.6%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		21 4.8%	8 5.4%
Week 81: very much	Number Analyzed	434 participants	148 participants
		5 1.2%	2 1.4%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		242 66.3%	72 75.8%
Week 97: a little	Number Analyzed	365 participants	95 participants
		100 27.4%	18 18.9%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		18 4.9%	4 4.2%
Week 97: very much	Number Analyzed	365 participants	95 participants
		5 1.4%	1 1.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		188 68.4%	54 74.0%
Week 113: a little	Number Analyzed	275 participants	73 participants
		71 25.8%	14 19.2%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		13 4.7%	3 4.1%
Week 113: very much	Number Analyzed	275 participants	93 participants
		3 1.1%	2 2.2%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		127 66.1%	25 61.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		55 28.6%	14 34.1%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		7 3.6%	1 2.4%
Week 129: very much	Number Analyzed	192 participants	41 participants
		3 1.6%	1 2.4%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		77 66.4%	11 52.4%
Week 145: a little	Number Analyzed	116 participants	21 participants
		34 29.3%	9 42.9%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		4 3.4%	1 4.8%
Week 145: very much	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		27 67.5%	2 25.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		10 25.0%	6 75.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		3 7.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		3 50.0%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

26. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 40
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 40 are reported. Question 40 was following: "Have your daily activities been limited by your bowel problems?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		758 85.7%	393 89.5%
Baseline: a little	Number Analyzed	884 participants	439 participants
		112 12.7%	40 9.1%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		9 1.0%	4 0.9%
Baseline: very much	Number Analyzed	884 participants	439 participants
		5 0.6%	2 0.5%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		707 84.3%	352 84.0%
Week 17: a little	Number Analyzed	839 participants	419 participants
		107 12.8%	57 13.6%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		19 2.3%	6 1.4%
Week 17: very much	Number Analyzed	839 participants	419 participants
		6 0.7%	4 1.0%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		621 84.3%	292 85.6%
Week 33: a little	Number Analyzed	737 participants	341 participants
		98 13.3%	40 11.7%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		14 1.9%	8 2.3%
Week 33: very much	Number Analyzed	737 participants	341 participants
		4 0.5%	1 0.3%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		525 82.7%	211 84.4%
Week 49: a little	Number Analyzed	635 participants	250 participants
		88 13.9%	29 11.6%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		20 3.1%	7 2.8%
Week 49: very much	Number Analyzed	635 participants	250 participants
		2 0.3%	3 1.2%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		441 82.3%	165 85.5%
Week 65: a little	Number Analyzed	536 participants	193 participants
		78 14.6%	24 12.4%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		11 2.1%	3 1.6%
Week 65: very much	Number Analyzed	536 participants	193 participants
		6 1.1%	1 0.5%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		360 82.9%	121 81.8%
Week 81: a little	Number Analyzed	434 participants	148 participants
		56 12.9%	23 15.5%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		17 3.9%	3 2.0%
Week 81: very much	Number Analyzed	434 participants	148 participants
		1 0.2%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		289 79.2%	84 88.4%
Week 97: a little	Number Analyzed	365 participants	95 participants
		58 15.9%	11 11.6%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		17 4.7%	0 0.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		1 0.3%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		219 79.6%	62 84.9%
Week 113: a little	Number Analyzed	275 participants	73 participants
		46 16.7%	11 15.1%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		8 2.9%	0 0.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		2 0.7%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		153 79.7%	36 87.8%
Week 129: a little	Number Analyzed	192 participants	41 participants
		33 17.2%	5 12.2%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		5 2.6%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		93 80.2%	17 81.0%
Week 145: a little	Number Analyzed	116 participants	21 participants
		19 16.4%	4 19.0%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		4 3.4%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		29 72.5%	8 100.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		9 22.5%	0 0.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		2 5.0%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		4 66.7%	1 100.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

27. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 41
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 41 are reported. Question 41 was following: "Have you had any unintentional release (leakage) of stools?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		794 89.8%	404 92.0%
Baseline: a little	Number Analyzed	884 participants	439 participants
		78 8.8%	32 7.3%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		11 1.2%	2 0.5%
Baseline: very much	Number Analyzed	884 participants	439 participants
		1 0.1%	1 0.2%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		751 89.5%	372 88.8%
Week 17: a little	Number Analyzed	839 participants	419 participants
		79 9.4%	43 10.3%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		8 1.0%	3 0.7%
Week 17: very much	Number Analyzed	839 participants	419 participants
		1 0.1%	1 0.2%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		638 86.6%	307 90.0%
Week 33: a little	Number Analyzed	737 participants	341 participants
		92 12.5%	32 9.4%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		4 0.5%	1 0.3%
Week 33: very much	Number Analyzed	737 participants	341 participants
		3 0.4%	1 0.3%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		554 87.2%	221 88.4%
Week 49: a little	Number Analyzed	635 participants	250 participants
		73 11.5%	25 10.0%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		5 0.8%	4 1.6%
Week 49: very much	Number Analyzed	635 participants	250 participants
		3 0.5%	0 0.0%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		467 87.1%	175 90.7%
Week 65: a little	Number Analyzed	536 participants	193 participants
		57 10.6%	16 8.3%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		9 1.7%	1 0.5%
Week 65: very much	Number Analyzed	536 participants	193 participants
		3 0.6%	1 0.5%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		380 87.6%	136 91.9%
Week 81: a little	Number Analyzed	434 participants	148 participants
		51 11.8%	12 8.1%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		2 0.5%	0 0.0%
Week 81: very much	Number Analyzed	434 participants	148 participants
		1 0.2%	0 0.0%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		315 86.3%	86 90.5%
Week 97: a little	Number Analyzed	365 participants	95 participants
		47 12.9%	9 9.5%
Week 97: quite a bit	Number Analyzed	933 participants	95 participants
		3 0.3%	0 0.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		233 84.7%	66 90.4%
Week 113: a little	Number Analyzed	275 participants	73 participants
		40 14.5%	7 9.6%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		2 0.7%	0 0.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		167 87.0%	39 95.1%
Week 129: a little	Number Analyzed	192 participants	41 participants
		25 13.0%	2 4.9%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		93 80.2%	20 95.2%
Week 145: a little	Number Analyzed	116 participants	21 participants
		22 19.0%	1 4.8%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		30 75.0%	8 100.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		9 22.5%	0 0.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		4 66.7%	1 100.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

28. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 42
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 42 are reported. Question 42 was following: "Have you had blood in your stools?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		836 94.6%	422 96.1%
Baseline: a little	Number Analyzed	884 participants	439 participants
		48 5.4%	17 3.9%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Baseline: very much	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		801 95.5%	399 95.2%
Week 17: a little	Number Analyzed	839 participants	419 participants
		36 4.3%	18 4.3%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		2 0.2%	2 0.5%
Week 17: very much	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		707 95.9%	330 96.8%
Week 33: a little	Number Analyzed	737 participants	341 participants
		29 3.9%	11 3.2%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		1 0.1%	0 0.0%
Week 33: very much	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		608 95.7%	245 98.0%
Week 49: a little	Number Analyzed	635 participants	250 participants
		27 4.3%	5 2.0%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 49: very much	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		514 95.9%	180 93.3%
Week 65: a little	Number Analyzed	536 participants	193 participants
		19 3.5%	13 6.7%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		3 0.6%	0 0.0%
Week 65: very much	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		420 96.8%	143 96.6%
Week 81: a little	Number Analyzed	434 participants	148 participants
		14 3.2%	4 2.7%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		0 0.0%	1 0.7%
Week 81: very much	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		357 97.8%	93 97.9%
Week 97: a little	Number Analyzed	365 participants	95 participants
		8 2.2%	2 2.1%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		262 95.3%	72 98.6%
Week 113: a little	Number Analyzed	275 participants	73 participants
		13 4.7%	1 1.4%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		186 96.9%	41 100.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		5 2.6%	0 0.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		114 98.3%	21 100.0%
Week 145: a little	Number Analyzed	116 participants	21 participants
		2 1.7%	0 0.0%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		38 95.0%	8 100.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		2 5.0%	0 0.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		6 100.0%	1 100.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

29. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 43
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 43 are reported. Question 43 was following: "Did you have a bloated feeling in your abdomen?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		667 75.5%	320 72.9%
Baseline: a little	Number Analyzed	884 participants	439 participants
		190 21.5%	103 23.5%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		22 2.5%	16 3.6%
Baseline: very much	Number Analyzed	884 participants	439 participants
		5 0.6%	0 0.0%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		601 71.6%	283 67.5%
Week 17: a little	Number Analyzed	839 participants	419 participants
		199 23.7%	121 28.9%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		31 3.7%	13 3.1%
Week 17: very much	Number Analyzed	839 participants	419 participants
		8 1.0%	2 0.5%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		526 71.4%	235 68.9%
Week 33: a little	Number Analyzed	737 participants	341 participants
		183 24.8%	95 27.9%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		22 3.0%	8 2.3%
Week 33: very much	Number Analyzed	737 participants	341 participants
		6 0.8%	3 0.9%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		449 70.7%	174 69.6%
Week 49: a little	Number Analyzed	635 participants	250 participants
		163 25.7%	63 25.2%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		20 3.1%	11 4.4%
Week 49: very much	Number Analyzed	635 participants	250 participants
		3 0.5%	2 0.8%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		381 71.1%	135 69.9%
Week 65: a little	Number Analyzed	536 participants	193 participants
		132 24.6%	51 26.4%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		19 3.5%	7 3.6%
Week 65: very much	Number Analyzed	536 participants	193 participants
		4 0.7%	0 0.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		304 70.0%	103 69.6%
Week 81: a little	Number Analyzed	434 participants	148 participants
		110 25.3%	44 29.7%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		18 4.1%	1 0.7%
Week 81: very much	Number Analyzed	434 participants	148 participants
		2 0.5%	0 0.0%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		258 70.7%	72 75.8%
Week 97: a little	Number Analyzed	365 participants	95 participants
		87 23.8%	23 24.2%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		19 5.2%	0 0.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		1 0.3%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		199 72.4%	55 75.3%
Week 113: a little	Number Analyzed	275 participants	73 participants
		66 24.0%	18 24.7%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		9 3.3%	0 0.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		1 0.4%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		139 72.4%	25 61.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		43 22.4%	16 39.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		8 4.2%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		2 1.0%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		87 75.0%	13 61.9%
Week 145: a little	Number Analyzed	116 participants	21 participants
		24 20.7%	8 38.1%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		4 3.4%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		33 82.5%	6 75.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		7 17.5%	2 25.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		4 66.7%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		2 33.3%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

30. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 44
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 44 are reported. Question 44 was following: "Did you have hot flushes?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		374 42.3%	177 40.3%
Baseline: a little	Number Analyzed	884 participants	439 participants
		314 35.5%	166 37.8%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		151 17.1%	68 15.5%
Baseline: very much	Number Analyzed	884 participants	439 participants
		45 5.1%	28 6.4%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		265 31.6%	182 43.4%
Week 17: a little	Number Analyzed	839 participants	419 participants
		311 37.1%	153 36.5%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		189 22.5%	62 14.8%
Week 17: very much	Number Analyzed	839 participants	419 participants
		74 8.8%	22 5.3%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		253 34.3%	144 42.2%
Week 33: a little	Number Analyzed	737 participants	341 participants
		268 36.4%	116 34.0%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		155 21.0%	60 17.6%
Week 33: very much	Number Analyzed	737 participants	341 participants
		61 8.3%	21 6.2%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		227 35.7%	112 44.8%
Week 49: a little	Number Analyzed	635 participants	250 participants
		235 37.0%	94 37.6%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		130 20.5%	30 12.0%
Week 49: very much	Number Analyzed	635 participants	250 participants
		43 6.8%	14 5.6%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		203 37.9%	79 40.9%
Week 65: a little	Number Analyzed	536 participants	193 participants
		194 36.2%	77 39.9%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		104 19.4%	30 15.5%
Week 65: very much	Number Analyzed	536 participants	193 participants
		35 6.5%	7 3.6%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		175 40.3%	69 46.6%
Week 81: a little	Number Analyzed	434 participants	148 participants
		157 36.2%	58 39.2%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		75 17.3%	16 10.8%
Week 81: very much	Number Analyzed	434 participants	148 participants
		27 6.2%	5 3.4%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		155 42.5%	48 50.5%
Week 97: a little	Number Analyzed	365 participants	95 participants
		126 34.5%	34 35.8%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		57 15.6%	12 12.6%
Week 97: very much	Number Analyzed	365 participants	95 participants
		27 7.4%	1 1.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		114 41.5%	33 45.2%
Week 113: a little	Number Analyzed	275 participants	73 participants
		102 37.1%	24 32.9%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		44 16.0%	14 19.2%
Week 113: very much	Number Analyzed	275 participants	73 participants
		15 5.5%	2 2.7%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		84 43.8%	22 53.7%
Week 129: a little	Number Analyzed	192 participants	41 participants
		74 38.5%	16 39.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		23 12.0%	3 7.3%
Week 129: very much	Number Analyzed	192 participants	41 participants
		11 5.7%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		45 38.8%	10 47.6%
Week 145: a little	Number Analyzed	116 participants	21 participants
		46 39.7%	10 47.6%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		18 15.5%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		7 6.0%	1 4.8%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		18 45.0%	3 37.5%
Week 161: a little	Number Analyzed	40 participants	8 participants
		14 35.0%	3 37.5%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		5 12.5%	2 25.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		3 7.5%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		1 16.7%	1 100.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

31. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 45
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 45 are reported. Question 45 was following: "Have you had sore or enlarged nipples or breasts?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		688 77.8%	333 75.9%
Baseline: a little	Number Analyzed	884 participants	439 participants
		146 16.5%	80 18.2%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		38 4.3%	24 5.5%
Baseline: very much	Number Analyzed	884 participants	439 participants
		12 1.4%	2 0.5%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		626 74.6%	315 75.2%
Week 17: a little	Number Analyzed	839 participants	419 participants
		160 19.1%	80 19.1%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		39 4.6%	18 4.3%
Week 17: very much	Number Analyzed	839 participants	419 participants
		14 1.7%	6 1.4%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		526 71.4%	260 76.2%
Week 33: a little	Number Analyzed	737 participants	341 participants
		164 22.3%	62 18.2%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		34 4.6%	15 4.4%
Week 33: very much	Number Analyzed	737 participants	341 participants
		13 1.8%	4 1.2%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		444 69.9%	188 75.2%
Week 49: a little	Number Analyzed	635 participants	250 participants
		138 21.7%	52 20.8%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		41 6.5%	5 2.0%
Week 49: very much	Number Analyzed	635 participants	250 participants
		12 1.9%	5 2.0%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		371 69.2%	149 77.2%
Week 65: a little	Number Analyzed	536 participants	193 participants
		119 22.2%	37 19.2%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		31 5.8%	7 3.6%
Week 65: very much	Number Analyzed	536 participants	193 participants
		15 2.8%	0 0.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		306 70.5%	115 77.7%
Week 81: a little	Number Analyzed	434 participants	148 participants
		84 19.4%	26 17.6%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		34 7.8%	6 4.1%
Week 81: very much	Number Analyzed	434 participants	148 participants
		10 2.3%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		239 65.5%	80 84.2%
Week 97: a little	Number Analyzed	365 participants	95 participants
		92 25.2%	13 13.7%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		30 8.2%	1 1.1%
Week 97: very much	Number Analyzed	365 participants	95 participants
		4 1.1%	1 1.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		190 69.1%	55 75.3%
Week 113: a little	Number Analyzed	275 participants	73 participants
		62 22.5%	12 16.4%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		19 6.9%	5 6.8%
Week 113: very much	Number Analyzed	275 participants	73 participants
		4 1.5%	1 1.4%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		128 66.7%	30 73.2%
Week 129: a little	Number Analyzed	192 participants	41 participants
		51 26.6%	8 19.5%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		9 4.7%	3 7.3%
Week 129: very much	Number Analyzed	192 participants	41 participants
		4 2.1%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		78 67.2%	17 81.0%
Week 145: a little	Number Analyzed	116 participants	21 participants
		29 25.0%	3 14.3%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		7 6.0%	1 4.8%
Week 145: very much	Number Analyzed	116 participants	21 participants
		2 1.7%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		26 65.0%	4 50.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		11 27.5%	3 37.5%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		2 5.0%	1 12.5%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		2 33.3%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

32. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 46
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 46 are reported. Question 46 was following: "Have you had swelling in your legs or ankles?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		663 75.0%	323 73.6%
Baseline: a little	Number Analyzed	884 participants	439 participants
		189 21.4%	89 20.3%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		22 2.5%	22 5.0%
Baseline: very much	Number Analyzed	884 participants	439 participants
		10 1.1%	5 1.1%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		625 74.5%	284 67.8%
Week 17: a little	Number Analyzed	839 participants	419 participants
		179 21.3%	112 26.7%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		30 3.6%	21 5.0%
Week 17: very much	Number Analyzed	839 participants	419 participants
		5 0.6%	2 0.5%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		530 71.9%	243 71.3%
Week 33: a little	Number Analyzed	737 participants	341 participants
		159 21.6%	76 22.3%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		41 5.6%	20 5.9%
Week 33: very much	Number Analyzed	737 participants	341 participants
		7 0.9%	2 0.6%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		453 71.3%	176 70.4%
Week 49: a little	Number Analyzed	635 participants	250 participants
		155 24.4%	58 23.2%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		23 3.6%	15 6.0%
Week 49: very much	Number Analyzed	635 participants	250 participants
		4 0.6%	1 0.4%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		378 70.5%	135 69.9%
Week 65: a little	Number Analyzed	536 participants	193 participants
		127 23.7%	48 24.9%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		27 5.0%	10 5.2%
Week 65: very much	Number Analyzed	536 participants	193 participants
		4 0.7%	0 0.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		301 69.4%	104 70.3%
Week 81: a little	Number Analyzed	434 participants	148 participants
		102 23.5%	36 24.3%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		27 6.2%	7 4.7%
Week 81: very much	Number Analyzed	434 participants	148 participants
		4 0.9%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		259 71.0%	69 72.6%
Week 97: a little	Number Analyzed	365 participants	95 participants
		79 21.6%	20 21.1%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		19 5.2%	5 5.3%
Week 97: very much	Number Analyzed	365 participants	95 participants
		8 2.2%	1 1.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		191 69.5%	40 54.8%
Week 113: a little	Number Analyzed	275 participants	73 participants
		65 23.6%	27 37.0%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		16 5.8%	6 8.2%
Week 113: very much	Number Analyzed	275 participants	73 participants
		3 1.1%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		134 69.8%	27 65.9%
Week 129: a little	Number Analyzed	192 participants	41 participants
		48 25.0%	14 34.1%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		8 4.2%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		2 1.0%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		76 65.5%	15 71.4%
Week 145: a little	Number Analyzed	116 participants	21 participants
		34 29.3%	5 23.8%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		5 4.3%	1 4.8%
Week 145: very much	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		31 77.5%	6 75.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		8 20.0%	2 25.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	1 100.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

33. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 47
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 47 are reported. Question 47 was following: "Has weight loss been a problem for you?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		820 92.8%	399 90.9%
Baseline: a little	Number Analyzed	884 participants	439 participants
		48 5.4%	25 5.7%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		10 1.1%	10 2.3%
Baseline: very much	Number Analyzed	884 participants	439 participants
		6 0.7%	5 1.1%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		733 87.4%	375 89.5%
Week 17: a little	Number Analyzed	839 participants	419 participants
		81 9.7%	28 6.7%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		15 1.8%	13 3.1%
Week 17: very much	Number Analyzed	839 participants	419 participants
		10 1.2%	3 0.7%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		643 87.2%	296 86.8%
Week 33: a little	Number Analyzed	737 participants	341 participants
		72 9.8%	35 10.3%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		13 1.8%	5 1.5%
Week 33: very much	Number Analyzed	737 participants	341 participants
		9 1.2%	5 1.5%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		553 87.1%	215 86.0%
Week 49: a little	Number Analyzed	635 participants	250 participants
		61 9.6%	29 11.6%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		15 2.4%	3 1.2%
Week 49: very much	Number Analyzed	635 participants	250 participants
		6 0.9%	3 1.2%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		479 89.4%	168 87.0%
Week 65: a little	Number Analyzed	536 participants	193 participants
		39 7.3%	20 10.4%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		11 2.1%	4 2.1%
Week 65: very much	Number Analyzed	536 participants	193 participants
		7 1.3%	1 0.5%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		371 85.5%	136 91.9%
Week 81: a little	Number Analyzed	434 participants	148 participants
		46 10.6%	10 6.8%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		14 3.2%	1 0.7%
Week 81: very much	Number Analyzed	434 participants	148 participants
		3 0.7%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		314 86.0%	84 88.4%
Week 97: a little	Number Analyzed	365 participants	95 participants
		36 9.9%	10 10.5%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		10 2.7%	0 0.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		5 1.4%	1 1.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		235 85.5%	62 84.9%
Week 113: a little	Number Analyzed	275 participants	73 participants
		27 9.8%	8 11.0%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		9 3.3%	1 1.4%
Week 113: very much	Number Analyzed	275 participants	73 participants
		4 1.5%	2 2.7%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		169 88.0%	37 90.2%
Week 129: a little	Number Analyzed	192 participants	41 participants
		17 8.9%	4 9.8%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		5 2.6%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		95 81.9%	20 95.2%
Week 145: a little	Number Analyzed	116 participants	21 participants
		17 14.7%	1 4.8%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		4 3.4%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		34 85.0%	8 100.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		5 12.5%	0 0.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		5 83.3%	1 100.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

34. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 48
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 48 are reported. Question 48 was following: "Has weight gain been a problem for you?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		677 76.6%	315 71.8%
Baseline: a little	Number Analyzed	884 participants	439 participants
		153 17.3%	95 21.6%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		40 4.5%	16 3.6%
Baseline: very much	Number Analyzed	884 participants	439 participants
		14 1.6%	13 3.0%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		674 80.3%	316 75.4%
Week 17: a little	Number Analyzed	839 participants	419 participants
		118 14.1%	74 17.7%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		30 3.6%	19 4.5%
Week 17: very much	Number Analyzed	839 participants	419 participants
		17 2.0%	10 2.4%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		570 77.3%	259 76.0%
Week 33: a little	Number Analyzed	737 participants	341 participants
		133 18.0%	59 17.3%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		21 2.8%	18 5.3%
Week 33: very much	Number Analyzed	737 participants	341 participants
		13 1.8%	5 1.5%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		479 75.4%	193 77.2%
Week 49: a little	Number Analyzed	635 participants	250 participants
		125 19.7%	44 17.6%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		18 2.8%	10 4.0%
Week 49: very much	Number Analyzed	635 participants	250 participants
		13 2.0%	3 1.2%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		410 76.5%	155 80.3%
Week 65: a little	Number Analyzed	536 participants	193 participants
		92 17.2%	27 14.0%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		26 4.9%	9 4.7%
Week 65: very much	Number Analyzed	536 participants	193 participants
		8 1.5%	2 1.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		327 75.3%	115 77.7%
Week 81: a little	Number Analyzed	434 participants	148 participants
		71 16.4%	27 18.2%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		28 6.5%	5 3.4%
Week 81: very much	Number Analyzed	434 participants	148 participants
		8 1.8%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		267 73.2%	76 80.0%
Week 97: a little	Number Analyzed	365 participants	95 participants
		70 19.2%	16 16.8%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		24 6.6%	2 2.1%
Week 97: very much	Number Analyzed	365 participants	95 participants
		4 1.1%	1 1.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		200 72.7%	60 82.2%
Week 113: a little	Number Analyzed	275 participants	73 participants
		56 20.4%	10 13.7%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		10 3.6%	3 4.1%
Week 113: very much	Number Analyzed	275 participants	73 participants
		9 3.3%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		156 81.3%	32 78.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		27 14.1%	8 19.5%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		5 2.6%	1 2.4%
Week 129: very much	Number Analyzed	192 participants	41 participants
		4 2.1%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		89 76.7%	16 76.2%
Week 145: a little	Number Analyzed	116 participants	21 participants
		18 15.5%	5 23.8%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		7 6.0%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		2 1.7%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		31 77.5%	6 75.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		6 15.0%	2 25.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		2 5.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		2 33.3%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		3 50.0%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

35. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 49
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 49 are reported. Question 49 was following: "Have you felt less masculine as a result of your illness or treatment?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		435 49.2%	214 48.7%
Baseline: a little	Number Analyzed	884 participants	439 participants
		234 26.5%	131 29.8%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		138 15.6%	59 13.4%
Baseline: very much	Number Analyzed	884 participants	439 participants
		77 8.7%	35 8.0%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		400 47.7%	210 50.1%
Week 17: a little	Number Analyzed	839 participants	419 participants
		244 29.1%	115 27.4%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		109 13.0%	57 13.6%
Week 17: very much	Number Analyzed	839 participants	419 participants
		86 10.3%	37 8.8%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		345 46.8%	167 49.0%
Week 33: a little	Number Analyzed	737 participants	341 participants
		207 28.1%	107 31.4%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		109 14.8%	38 11.1%
Week 33: very much	Number Analyzed	737 participants	341 participants
		76 10.3%	29 8.5%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		302 47.6%	127 50.8%
Week 49: a little	Number Analyzed	635 participants	250 participants
		187 29.4%	68 27.2%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		84 13.2%	36 14.4%
Week 49: very much	Number Analyzed	635 participants	250 participants
		62 9.8%	19 7.6%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		263 49.1%	90 46.6%
Week 65: a little	Number Analyzed	536 participants	193 participants
		142 26.5%	57 29.5%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		71 13.2%	24 12.4%
Week 65: very much	Number Analyzed	536 participants	193 participants
		60 11.2%	22 11.4%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		206 47.5%	74 50.0%
Week 81: a little	Number Analyzed	434 participants	148 participants
		124 28.6%	38 25.7%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		57 13.1%	17 11.5%
Week 81: very much	Number Analyzed	434 participants	148 participants
		47 10.8%	19 12.8%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		175 47.9%	46 48.4%
Week 97: a little	Number Analyzed	365 participants	95 participants
		98 26.8%	28 29.5%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		47 12.9%	10 10.5%
Week 97: very much	Number Analyzed	365 participants	95 participants
		45 12.3%	11 11.6%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		136 49.5%	31 42.5%
Week 113: a little	Number Analyzed	275 participants	73 participants
		78 28.4%	27 37.0%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		30 10.9%	8 11.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		31 11.3%	7 9.6%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		91 47.4%	18 43.9%
Week 129: a little	Number Analyzed	192 participants	41 participants
		49 25.5%	16 39.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		27 14.1%	5 12.2%
Week 129: very much	Number Analyzed	192 participants	41 participants
		25 13.0%	2 4.9%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		59 50.9%	9 42.9%
Week 145: a little	Number Analyzed	116 participants	21 participants
		31 26.7%	9 42.9%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		18 15.5%	1 4.8%
Week 145: very much	Number Analyzed	116 participants	21 participants
		8 6.9%	2 9.5%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		18 45.0%	2 25.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		15 37.5%	3 37.5%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		3 7.5%	1 12.5%
Week 161: very much	Number Analyzed	40 participants	8 participants
		4 10.0%	2 25.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		3 50.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		3 50.0%	1 100.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

36. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 50
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 50 are reported. Question 50 was following: "To what extent were you interested in sex?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		586 66.3%	291 66.3%
Baseline: a little	Number Analyzed	884 participants	439 participants
		204 23.1%	101 23.0%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		67 7.6%	32 7.3%
Baseline: very much	Number Analyzed	884 participants	439 participants
		27 3.1%	15 3.4%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		637 75.9%	293 69.9%
Week 17: a little	Number Analyzed	839 participants	419 participants
		136 16.2%	92 22.0%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		45 5.4%	20 4.8%
Week 17: very much	Number Analyzed	839 participants	419 participants
		21 2.5%	14 3.3%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		542 73.5%	251 73.6%
Week 33: a little	Number Analyzed	737 participants	341 participants
		136 18.5%	66 19.4%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		37 5.0%	18 5.3%
Week 33: very much	Number Analyzed	737 participants	341 participants
		22 3.0%	6 1.8%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		483 76.1%	180 72.0%
Week 49: a little	Number Analyzed	635 participants	250 participants
		106 16.7%	50 20.0%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		33 5.2%	12 4.8%
Week 49: very much	Number Analyzed	635 participants	250 participants
		13 2.0%	8 3.2%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		417 77.8%	143 74.1%
Week 65: a little	Number Analyzed	536 participants	193 participants
		78 14.6%	37 19.2%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		27 5.0%	9 4.7%
Week 65: very much	Number Analyzed	536 participants	193 participants
		14 2.6%	4 2.1%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		320 73.7%	114 77.0%
Week 81: a little	Number Analyzed	434 participants	148 participants
		76 17.5%	24 16.2%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		26 6.0%	9 6.1%
Week 81: very much	Number Analyzed	434 participants	148 participants
		12 2.8%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		286 78.4%	65 68.4%
Week 97: a little	Number Analyzed	365 participants	95 participants
		52 14.2%	19 20.0%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		20 5.5%	8 8.4%
Week 97: very much	Number Analyzed	365 participants	95 participants
		7 1.9%	3 3.2%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		218 79.3%	59 80.8%
Week 113: a little	Number Analyzed	275 participants	73 participants
		36 13.1%	11 15.1%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		14 5.1%	1 1.4%
Week 113: very much	Number Analyzed	275 participants	73 participants
		7 2.5%	2 2.7%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		156 81.3%	33 80.5%
Week 129: a little	Number Analyzed	192 participants	41 participants
		24 12.5%	6 14.6%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		9 4.7%	2 4.9%
Week 129: very much	Number Analyzed	192 participants	41 participants
		3 1.6%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		92 79.3%	14 66.7%
Week 145: a little	Number Analyzed	116 participants	21 participants
		16 13.8%	3 14.3%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		7 6.0%	4 19.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		30 75.0%	5 62.5%
Week 161: a little	Number Analyzed	40 participants	8 participants
		5 12.5%	2 25.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		4 10.0%	1 12.5%
Week 161: very much	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		4 66.7%	1 100.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

37. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 51
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 51 are reported. Question 51 was following: "To what extent were you sexually active (with or without intercourse)?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	884 participants	439 participants
		735 83.1%	374 85.2%
Baseline: a little	Number Analyzed	884 participants	439 participants
		98 11.1%	38 8.7%
Baseline: quite a bit	Number Analyzed	884 participants	439 participants
		41 4.6%	19 4.3%
Baseline: very much	Number Analyzed	884 participants	439 participants
		10 1.1%	8 1.8%
Baseline: not answered	Number Analyzed	884 participants	439 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		734 87.5%	354 84.5%
Week 17: a little	Number Analyzed	839 participants	419 participants
		71 8.5%	44 10.5%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		24 2.9%	13 3.1%
Week 17: very much	Number Analyzed	839 participants	419 participants
		10 1.2%	8 1.9%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		0 0.0%	0 0.0%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		642 87.1%	299 87.7%
Week 33: a little	Number Analyzed	737 participants	341 participants
		68 9.2%	28 8.2%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		20 2.7%	9 2.6%
Week 33: very much	Number Analyzed	737 participants	341 participants
		7 0.9%	5 1.5%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		0 0.0%	0 0.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		569 89.6%	214 85.6%
Week 49: a little	Number Analyzed	635 participants	250 participants
		46 7.2%	26 10.4%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		15 2.4%	6 2.4%
Week 49: very much	Number Analyzed	635 participants	250 participants
		5 0.8%	4 1.6%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		0 0.0%	0 0.0%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		485 90.5%	170 88.1%
Week 65: a little	Number Analyzed	536 participants	193 participants
		37 6.9%	14 7.3%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		12 2.2%	7 3.6%
Week 65: very much	Number Analyzed	536 participants	193 participants
		2 0.4%	2 1.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		0 0.0%	0 0.0%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		381 87.8%	130 87.8%
Week 81: a little	Number Analyzed	434 participants	148 participants
		32 7.4%	13 8.8%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		15 3.5%	5 3.4%
Week 81: very much	Number Analyzed	434 participants	148 participants
		6 1.4%	0 0.0%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		333 91.2%	79 83.2%
Week 97: a little	Number Analyzed	365 participants	95 participants
		20 5.5%	12 12.6%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		9 2.5%	4 4.2%
Week 97: very much	Number Analyzed	365 participants	95 participants
		3 0.8%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		0 0.0%	0 0.0%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		250 90.9%	68 93.2%
Week 113: a little	Number Analyzed	275 participants	73 participants
		16 5.8%	3 4.1%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		6 2.2%	2 2.7%
Week 113: very much	Number Analyzed	275 participants	73 participants
		3 1.1%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		176 91.7%	37 90.2%
Week 129: a little	Number Analyzed	192 participants	41 participants
		8 4.2%	3 7.3%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		5 2.6%	1 2.4%
Week 129: very much	Number Analyzed	192 participants	41 participants
		3 1.6%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		106 91.4%	17 81.0%
Week 145: a little	Number Analyzed	116 participants	21 participants
		4 3.4%	3 14.3%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		5 4.3%	1 4.8%
Week 145: very much	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		35 87.5%	6 75.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		3 7.5%	2 25.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		5 83.3%	1 100.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		1 16.7%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%

38. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 52
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 52 are reported. Question 52 was following: "To what extent was sex enjoyable for you?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	50 participants	24 participants
		5 10.0%	6 25.0%
Baseline: a little	Number Analyzed	50 participants	24 participants
		23 46.0%	11 45.8%
Baseline: quite a bit	Number Analyzed	50 participants	24 participants
		14 28.0%	5 20.8%
Baseline: very much	Number Analyzed	50 participants	24 participants
		8 16.0%	2 8.3%
Baseline: not answered	Number Analyzed	50 participants	24 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		7 0.8%	3 0.7%
Week 17: a little	Number Analyzed	839 participants	419 participants
		13 1.5%	9 2.1%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		16 1.9%	11 2.6%
Week 17: very much	Number Analyzed	839 participants	419 participants
		3 0.4%	4 1.0%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		800 95.4%	392 93.6%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		8 1.1%	4 1.2%
Week 33: a little	Number Analyzed	737 participants	341 participants
		17 2.3%	8 2.3%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		11 1.5%	5 1.5%
Week 33: very much	Number Analyzed	737 participants	341 participants
		4 0.5%	0 0.0%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		697 94.6%	324 95.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		3 0.5%	4 1.6%
Week 49: a little	Number Analyzed	635 participants	250 participants
		6 0.9%	5 2.0%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		9 1.4%	5 2.0%
Week 49: very much	Number Analyzed	635 participants	250 participants
		3 0.5%	4 1.6%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		614 96.7%	232 92.8%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		4 0.7%	2 1.0%
Week 65: a little	Number Analyzed	536 participants	193 participants
		6 1.1%	4 2.1%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		9 1.7%	4 2.1%
Week 65: very much	Number Analyzed	536 participants	193 participants
		3 0.6%	0 0.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		514 95.9%	183 94.8%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		5 1.2%	2 1.4%
Week 81: a little	Number Analyzed	434 participants	148 participants
		7 1.6%	3 2.0%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		4 0.9%	2 1.4%
Week 81: very much	Number Analyzed	434 participants	148 participants
		5 1.2%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		413 95.2%	140 94.6%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		2 0.5%	2 2.1%
Week 97: a little	Number Analyzed	365 participants	95 participants
		5 1.4%	0 0.0%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		3 0.8%	3 3.2%
Week 97: very much	Number Analyzed	365 participants	95 participants
		3 0.8%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		352 96.4%	90 94.7%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		0 0.0%	1 1.4%
Week 113: a little	Number Analyzed	275 participants	73 participants
		5 1.8%	1 1.4%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		2 0.7%	0 0.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		2 0.7%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		266 96.7%	71 97.3%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		188 97.9%	41 100.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: a little	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		1 0.9%	1 4.8%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		114 98.3%	20 95.2%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		38 95.0%	8 100.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		6 100.0%	1 100.0%

39. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 53
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 53 are reported. Question 53 was following: "Did you have difficulty getting or maintaining an erection?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	50 participants	24 participants
		6 12.0%	4 16.7%
Baseline: a little	Number Analyzed	50 participants	24 participants
		19 38.0%	5 20.8%
Baseline: quite a bit	Number Analyzed	50 participants	24 participants
		4 8.0%	4 16.7%
Baseline: very much	Number Analyzed	50 participants	24 participants
		21 42.0%	11 45.8%
Baseline: not answered	Number Analyzed	50 participants	24 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		10 1.2%	8 1.9%
Week 17: a little	Number Analyzed	839 participants	419 participants
		8 1.0%	8 1.9%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		8 1.0%	4 1.0%
Week 17: very much	Number Analyzed	839 participants	419 participants
		13 1.5%	7 1.7%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		800 95.4%	392 93.6%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		6 0.8%	2 0.6%
Week 33: a little	Number Analyzed	737 participants	341 participants
		8 1.1%	6 1.8%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		8 1.1%	3 0.9%
Week 33: very much	Number Analyzed	737 participants	341 participants
		18 2.4%	6 1.8%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		697 94.6%	324 95.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		4 0.6%	6 2.4%
Week 49: a little	Number Analyzed	635 participants	250 participants
		6 0.9%	5 2.0%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		0 0.0%	1 0.4%
Week 49: very much	Number Analyzed	635 participants	250 participants
		11 1.7%	6 2.4%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		614 96.7%	232 92.8%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		3 0.6%	1 0.5%
Week 65: a little	Number Analyzed	536 participants	193 participants
		4 0.7%	4 2.1%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		4 0.7%	2 1.0%
Week 65: very much	Number Analyzed	536 participants	193 participants
		11 2.1%	3 1.6%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		514 95.9%	183 94.8%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		7 1.6%	3 2.0%
Week 81: a little	Number Analyzed	434 participants	148 participants
		2 0.5%	2 1.4%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		3 0.7%	2 1.4%
Week 81: very much	Number Analyzed	434 participants	148 participants
		9 2.1%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		413 95.2%	140 94.6%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		2 0.5%	1 1.1%
Week 97: a little	Number Analyzed	365 participants	95 participants
		5 1.4%	1 1.1%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		1 0.3%	1 1.1%
Week 97: very much	Number Analyzed	365 participants	95 participants
		5 1.4%	2 2.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		352 96.4%	90 94.7%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		1 0.4%	0 0.0%
Week 113: a little	Number Analyzed	275 participants	73 participants
		3 1.1%	1 1.4%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		1 0.4%	0 0.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		4 1.5%	1 1.4%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		266 96.7%	71 97.3%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		3 1.6%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		188 97.9%	41 100.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: a little	Number Analyzed	116 participants	21 participants
		0 0.0%	1 4.8%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		1 0.9%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		114 98.3%	20 95.2%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		38 95.0%	8 100.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		6 100.0%	1 100.0%

40. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 54
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 54 are reported. Question 54 was following: "Did you have ejaculation problems (e.g, dry ejaculation)?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	50 participants	24 participants
		11 22.0%	7 29.2%
Baseline: a little	Number Analyzed	50 participants	24 participants
		14 28.0%	4 16.7%
Baseline: quite a bit	Number Analyzed	50 participants	24 participants
		3 6.0%	2 8.3%
Baseline: very much	Number Analyzed	50 participants	24 participants
		22 44.0%	11 45.8%
Baseline: not answered	Number Analyzed	50 participants	24 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		13 1.5%	11 2.6%
Week 17: a little	Number Analyzed	839 participants	419 participants
		5 0.6%	5 1.2%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		3 0.4%	1 0.2%
Week 17: very much	Number Analyzed	839 participants	419 participants
		18 2.1%	10 2.4%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		800 95.4%	392 93.6%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		12 1.6%	10 2.9%
Week 33: a little	Number Analyzed	737 participants	341 participants
		9 1.2%	1 0.3%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		5 0.7%	0 0.0%
Week 33: very much	Number Analyzed	737 participants	341 participants
		14 1.9%	6 1.8%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		697 94.6%	324 95.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		7 1.1%	6 2.4%
Week 49: a little	Number Analyzed	635 participants	250 participants
		3 0.5%	5 2.0%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		1 0.2%	1 0.4%
Week 49: very much	Number Analyzed	635 participants	250 participants
		10 1.6%	6 2.4%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		614 96.7%	232 92.8%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		8 1.5%	3 1.6%
Week 65: a little	Number Analyzed	536 participants	193 participants
		2 0.4%	1 0.5%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		1 0.2%	2 1.0%
Week 65: very much	Number Analyzed	536 participants	193 participants
		11 2.1%	4 2.1%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		514 95.9%	183 94.8%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		7 1.6%	4 2.7%
Week 81: a little	Number Analyzed	434 participants	148 participants
		0 0.0%	0 0.0%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		3 0.7%	0 0.0%
Week 81: very much	Number Analyzed	434 participants	148 participants
		11 2.5%	4 2.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		413 95.2%	140 94.6%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		5 1.4%	2 2.1%
Week 97: a little	Number Analyzed	365 participants	95 participants
		3 0.8%	0 0.0%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		0 0.0%	1 1.1%
Week 97: very much	Number Analyzed	365 participants	95 participants
		5 1.4%	2 2.1%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		352 96.4%	90 94.7%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		3 1.1%	2 2.7%
Week 113: a little	Number Analyzed	275 participants	73 participants
		1 0.4%	0 0.0%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		5 1.8%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		266 96.7%	71 97.3%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		3 1.6%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		188 97.9%	41 100.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		2 1.7%	0 0.0%
Week 145: a little	Number Analyzed	116 participants	21 participants
		0 0.0%	1 4.8%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		114 98.3%	20 95.2%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		38 95.0%	8 100.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		6 100.0%	1 100.0%

41. Secondary Outcome

Title	Number of Participants With European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Module Score for Question 55
Description	The EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It consisted of 25 questions (Question 31 to 55) distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions using 4 point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Number of participants with various responses to the question 55 are reported. Question 55 was following: "Have you felt uncomfortable about being sexually intimate?"
Time Frame	Baseline, Weeks 17, 33, 49, 65, 81, 97, 113, 129, 145,161 and 177

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all participants randomly assigned to study treatment and was based on randomized treatment assignment regardless of whether or not treatment was administered. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified categories.

Arm/Group Title		Enzalutamide 160 mg	Placebo
Arm/Group Description:		Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed		933	468
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline: not at all	Number Analyzed	50 participants	24 participants
		31 62.0%	13 54.2%
Baseline: a little	Number Analyzed	50 participants	24 participants
		13 26.0%	8 33.3%
Baseline: quite a bit	Number Analyzed	50 participants	24 participants
		4 8.0%	0 0.0%
Baseline: very much	Number Analyzed	50 participants	24 participants
		2 4.0%	3 12.5%
Baseline: not answered	Number Analyzed	50 participants	24 participants
		0 0.0%	0 0.0%
Week 17: not at all	Number Analyzed	839 participants	419 participants
		23 2.7%	14 3.3%
Week 17: a little	Number Analyzed	839 participants	419 participants
		11 1.3%	7 1.7%
Week 17: quite a bit	Number Analyzed	839 participants	419 participants
		2 0.2%	3 0.7%
Week 17: very much	Number Analyzed	839 participants	419 participants
		3 0.4%	3 0.7%
Week 17: not answered	Number Analyzed	839 participants	419 participants
		800 95.4%	392 93.6%
Week 33: not at all	Number Analyzed	737 participants	341 participants
		24 3.3%	10 2.9%
Week 33: a little	Number Analyzed	737 participants	341 participants
		6 0.8%	4 1.2%
Week 33: quite a bit	Number Analyzed	737 participants	341 participants
		6 0.8%	2 0.6%
Week 33: very much	Number Analyzed	737 participants	341 participants
		4 0.5%	1 0.3%
Week 33: not answered	Number Analyzed	737 participants	341 participants
		697 94.6%	324 95.0%
Week 49: not at all	Number Analyzed	635 participants	250 participants
		16 2.5%	10 4.0%
Week 49: a little	Number Analyzed	635 participants	250 participants
		4 0.6%	6 2.4%
Week 49: quite a bit	Number Analyzed	635 participants	250 participants
		1 0.2%	1 0.4%
Week 49: very much	Number Analyzed	635 participants	250 participants
		0 0.0%	1 0.4%
Week 49: not answered	Number Analyzed	635 participants	250 participants
		614 96.7%	232 92.8%
Week 65: not at all	Number Analyzed	536 participants	193 participants
		13 2.4%	5 2.6%
Week 65: a little	Number Analyzed	536 participants	193 participants
		7 1.3%	3 1.6%
Week 65: quite a bit	Number Analyzed	536 participants	193 participants
		1 0.2%	2 1.0%
Week 65: very much	Number Analyzed	536 participants	193 participants
		1 0.2%	0 0.0%
Week 65: not answered	Number Analyzed	536 participants	193 participants
		514 95.9%	183 94.8%
Week 81: not at all	Number Analyzed	434 participants	148 participants
		13 3.0%	5 3.4%
Week 81: a little	Number Analyzed	434 participants	148 participants
		6 1.4%	1 0.7%
Week 81: quite a bit	Number Analyzed	434 participants	148 participants
		1 0.2%	1 0.7%
Week 81: very much	Number Analyzed	434 participants	148 participants
		1 0.2%	1 0.7%
Week 81: not answered	Number Analyzed	434 participants	148 participants
		413 95.2%	140 94.6%
Week 97: not at all	Number Analyzed	365 participants	95 participants
		8 2.2%	3 3.2%
Week 97: a little	Number Analyzed	365 participants	95 participants
		3 0.8%	2 2.1%
Week 97: quite a bit	Number Analyzed	365 participants	95 participants
		1 0.3%	0 0.0%
Week 97: very much	Number Analyzed	365 participants	95 participants
		1 0.3%	0 0.0%
Week 97: not answered	Number Analyzed	365 participants	95 participants
		352 96.4%	90 94.7%
Week 113: not at all	Number Analyzed	275 participants	73 participants
		7 2.5%	2 2.7%
Week 113: a little	Number Analyzed	275 participants	73 participants
		0 0.0%	0 0.0%
Week 113: quite a bit	Number Analyzed	275 participants	73 participants
		1 0.4%	0 0.0%
Week 113: very much	Number Analyzed	275 participants	73 participants
		1 0.4%	0 0.0%
Week 113: not answered	Number Analyzed	275 participants	73 participants
		266 96.7%	71 97.3%
Week 129: not at all	Number Analyzed	192 participants	41 participants
		3 1.6%	0 0.0%
Week 129: a little	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: quite a bit	Number Analyzed	192 participants	41 participants
		1 0.5%	0 0.0%
Week 129: very much	Number Analyzed	192 participants	41 participants
		0 0.0%	0 0.0%
Week 129: not answered	Number Analyzed	192 participants	41 participants
		188 97.9%	41 100.0%
Week 145: not at all	Number Analyzed	116 participants	21 participants
		2 1.7%	1 4.8%
Week 145: a little	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: quite a bit	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: very much	Number Analyzed	116 participants	21 participants
		0 0.0%	0 0.0%
Week 145: not answered	Number Analyzed	116 participants	21 participants
		114 98.3%	20 95.2%
Week 161: not at all	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: a little	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: quite a bit	Number Analyzed	40 participants	8 participants
		1 2.5%	0 0.0%
Week 161: very much	Number Analyzed	40 participants	8 participants
		0 0.0%	0 0.0%
Week 161: not answered	Number Analyzed	40 participants	8 participants
		38 95.0%	8 100.0%
Week 177: not at all	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: a little	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: quite a bit	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: very much	Number Analyzed	6 participants	1 participants
		0 0.0%	0 0.0%
Week 177: not answered	Number Analyzed	6 participants	1 participants
		6 100.0%	1 100.0%

42. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug through the date of last dose +30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first). AEs included both non-serious adverse events (AEs) and SAEs.
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	930	465
Measure Type: Count of Participants; Unit of Measure: Participants
AEs	808 86.9%	360 77.4%
SAEs	226 24.3%	85 18.3%

43. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events Greater Than or Equal to Grade 3, Based on National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE), Version 4.0
Description	An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug through the date of last dose +30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first).Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported.
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	930	465
Measure Type: Count of Participants; Unit of Measure: Participants
	292 31.4%	109 23.4%

44. Secondary Outcome

Title	Number of Participants With Discontinuations From Study Treatment Due to Adverse Events (AEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both non-serious adverse events (AEs) and SAEs.
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	930	465
Measure Type: Count of Participants; Unit of Measure: Participants
	87 9.4%	28 6.0%

45. Secondary Outcome

Title	Number of Participants With Increase of 2 or More National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) (Version 4.0) Toxicity Grades Above Baseline - Hematology
Description	Hematology parameters: Haemoglobin (grams per liter [g/L]); leukocytes (log 10 raised to power 9 per liter [10*9/L]); lymphocytes (log 10 raised to power 6 per liter [10*6/L]); neutrophils (log 10 raised to power 6 per liter [10*6/L]); platelets (log 10 raised to power 9 per litre [10*9/L]).
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	930	465
Measure Type: Count of Participants; Unit of Measure: Participants
Haemoglobin (Low)	12 1.3%	7 1.5%
Leukocytes (Low)	7 0.8%	7 1.5%
Lymphocytes (High)	4 0.4%	2 0.4%
Lymphocytes (Low)	44 4.7%	26 5.6%
Neutrophils (Low)	13 1.4%	4 0.9%
Platelets (Low)	3 0.3%	2 0.4%

46. Secondary Outcome

Title	Number of Participants With Increase of 2 or More National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) (Version 4.0) Toxicity Grades Above Baseline - Chemistry
Description	Chemistry parameters: Alanine aminotransferase (units per liter [U/L]); albumin (g/L); alkaline phosphatase (U/L); bilirubin (micromoles per liter [umol/L]); calcium (millimoles per liter [mmol/L]); creatine kinase (U/L); creatinine (umol/L); glucose, magnesium, phosphate, potassium, sodium (mmol/L).
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	930	465
Measure Type: Count of Participants; Unit of Measure: Participants
Alanine Aminotransferase (High)	4 0.4%	1 0.2%
Albumin (Low)	7 0.8%	0 0.0%
Alkaline Phosphatase (High)	3 0.3%	6 1.3%
Aspartate Aminotransferase (High)	3 0.3%	1 0.2%
Bilirubin (High)	4 0.4%	1 0.2%
Calcium (High)	1 0.1%	1 0.2%
Calcium (Low)	2 0.2%	1 0.2%
Creatine Kinase (High)	4 0.4%	3 0.6%
Creatinine (High)	1 0.1%	7 1.5%
Glucose (High)	26 2.8%	8 1.7%
Glucose (Low)	5 0.5%	1 0.2%
Magnesium (High)	1 0.1%	0 0.0%
Magnesium (Low)	1 0.1%	0 0.0%
Phosphate (Low)	30 3.2%	13 2.8%
Potassium (High)	14 1.5%	5 1.1%
Potassium (Low)	0 0.0%	3 0.6%
Sodium (High)	2 0.2%	1 0.2%
Sodium (Low)	12 1.3%	7 1.5%

47. Secondary Outcome

Title	Number of Participants With Clinically Significant Vital Signs
Description	Vital signs included Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and heart rate.
Time Frame	From first dose of study drug to the last dose + 30 days (or the day before initiation of a new antineoplastic treatment, whichever occurred first) (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Outcome Measure Data

Analysis Population Description

The safety population was defined as all participants randomly assigned to receive at least 1 dose or partial dose of study drug (enzalutamide or placebo) according to the actual treatment received (not the treatment assigned).

Arm/Group Title	Enzalutamide 160 mg	Placebo
Arm/Group Description:	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
Overall Number of Participants Analyzed	930	465
Measure Type: Count of Participants; Unit of Measure: Participants
SBP	738 79.4%	328 70.5%
DBP	563 60.5%	229 49.2%
Heart rate	7 0.8%	4 0.9%

Adverse Events

Time Frame	Baseline up to 30 days after last dose of study drug or till death, whichever occurred first (up to a maximum duration of 69.8 months)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Data reported in this section was collected and analyzed only for participants who were treated with at least 1 dose of study drug.
Arm/Group Title	Enzalutamide 160 mg	Placebo	Placebo Patients Crossover to Enzalutamide 160 mg
Arm/Group Description	Participants received 4 capsules of Enzalutamide 40 mg each (total dose 160 mg per day) orally, once daily in double-blind and open-label phase (up to a maximum of 68.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days, and were long term followed up (for survival status and new prostate cancer therapies) from last dose to the death date or last known survival date.	Participants received 4 capsules of placebo (matched to Enzalutamide) orally, once daily in double blind phase (up to a maximum of 51.3 months) until radiographic progression. Participants were given an opportunity to switch to open-label enzalutamide after completion of double blind phase. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.	Participants who received placebo in double-blind phase and who agreed to proceed to open-label phase, received 4 capsules of Enzalutamide 40 mg each (total dose of 160 mg per day), orally once daily (up to a maximum of 18.8 months) until radiographic progression. Participants after last dose of study drug, were followed up for safety up to 30 days and were long term followed up (for survival status and new prostate cancer therapies) to the death date or last known survival date.
All-Cause Mortality
	Enzalutamide 160 mg	Placebo	Placebo Patients Crossover to Enzalutamide 160 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	285/930 (30.65%)	173/465 (37.20%)	4/87 (4.60%)
Serious Adverse Events
	Enzalutamide 160 mg	Placebo	Placebo Patients Crossover to Enzalutamide 160 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	372/930 (40.00%)	100/465 (21.51%)	12/87 (13.79%)
Blood and lymphatic system disorders
Anaemia * 1	10/930 (1.08%)	1/465 (0.22%)	1/87 (1.15%)
Anaemia macrocytic * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Haemolytic anaemia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Thrombocytopenia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Neutropenia * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Normochromic normocytic anaemia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Splenic haemorrhage * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cardiac disorders
Acute coronary syndrome * 1	6/930 (0.65%)	2/465 (0.43%)	0/87 (0.00%)
Acute myocardial infarction * 1	10/930 (1.08%)	2/465 (0.43%)	1/87 (1.15%)
Angina pectoris * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Angina unstable * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Aortic valve incompetence * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Aortic valve stenosis * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Arrhythmia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Atrial fibrillation * 1	9/930 (0.97%)	3/465 (0.65%)	0/87 (0.00%)
Atrial flutter * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Atrioventricular block complete * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Bradycardia * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Cardiac arrest * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Cardiac failure * 1	10/930 (1.08%)	0/465 (0.00%)	0/87 (0.00%)
Cardio-respiratory arrest * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Conduction disorder * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Coronary artery disease * 1	8/930 (0.86%)	0/465 (0.00%)	0/87 (0.00%)
Left ventricular failure * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Mitral valve incompetence * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Myocardial infarction * 1	10/930 (1.08%)	0/465 (0.00%)	0/87 (0.00%)
Myocardial ischaemia * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Pericardial effusion * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Right ventricular failure * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Sick sinus syndrome * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Sinus bradycardia * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Ventricular arrhythmia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Ventricular extrasystoles * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Atrioventricular block second degree * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cardiac aneurysm * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cardiac failure acute * 1	0/930 (0.00%)	0/465 (0.00%)	1/87 (1.15%)
Cardiac failure congestive * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cardiogenic shock * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cardiovascular insufficiency * 1	0/930 (0.00%)	0/465 (0.00%)	1/87 (1.15%)
Left ventricular dysfunction * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pericarditis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Sinus arrest * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Tricuspid valve disease * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Ventricular tachycardia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Congenital, familial and genetic disorders
Phimosis * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Ear and labyrinth disorders
Vertigo * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Eye disorders
Cataract * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Gastrointestinal disorders
Abdominal hernia * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Abdominal pain * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Acquired oesophageal web * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Constipation * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Diarrhoea * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Duodenal stenosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Duodenal ulcer haemorrhage * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Dysphagia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Faecaloma * 1	1/930 (0.11%)	2/465 (0.43%)	0/87 (0.00%)
Gastric haemorrhage * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Gastrointestinal mucosal disorder * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Hiatus hernia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Ileus * 1	3/930 (0.32%)	1/465 (0.22%)	0/87 (0.00%)
Inguinal hernia * 1	4/930 (0.43%)	3/465 (0.65%)	0/87 (0.00%)
Intestinal congestion * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Intestinal ischaemia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Large intestinal stenosis * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Melaena * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Mesenteric vein thrombosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Nausea * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Oesophageal varices haemorrhage * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Peptic ulcer * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Peptic ulcer haemorrhage * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Pharyngo-oesophageal diverticulum * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Small intestinal haemorrhage * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Small intestinal obstruction * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Upper gastrointestinal haemorrhage * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Rectal haemorrhage * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Abdominal distension * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Colitis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Colonic pseudo-obstruction * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Gastritis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Gastrointestinal haemorrhage * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Gastrointestinal necrosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Inguinal hernia strangulated * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Intestinal obstruction * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Lower gastrointestinal haemorrhage * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Periproctitis * 1	0/930 (0.00%)	0/465 (0.00%)	1/87 (1.15%)
Volvulus * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
General disorders
Asthenia * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Chest pain * 1	7/930 (0.75%)	1/465 (0.22%)	0/87 (0.00%)
Death * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Device occlusion * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Disease progression * 1	3/930 (0.32%)	0/465 (0.00%)	1/87 (1.15%)
Fatigue * 1	4/930 (0.43%)	1/465 (0.22%)	0/87 (0.00%)
General physical health deterioration * 1	3/930 (0.32%)	0/465 (0.00%)	1/87 (1.15%)
Non-cardiac chest pain * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Oedema peripheral * 1	0/930 (0.00%)	2/465 (0.43%)	0/87 (0.00%)
Pain * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Pyrexia * 1	3/930 (0.32%)	2/465 (0.43%)	0/87 (0.00%)
Stent-graft endoleak * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Sudden death * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Vessel puncture site haematoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Malaise * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Performance status decreased * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Sudden cardiac death * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Swelling * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Hepatobiliary disorders
Cholangitis acute * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Cholecystitis * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Cholecystitis acute * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Cholelithiasis * 1	4/930 (0.43%)	0/465 (0.00%)	0/87 (0.00%)
Hepatic cirrhosis * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Hepatic failure * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Bile duct stone * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Biliary colic * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cholelithiasis obstructive * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Hepatic function abnormal * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Immune system disorders
Anaphylactic reaction * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Anaphylactic shock * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Iodine allergy * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Infections and infestations
Appendicitis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Arthritis bacterial * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Bacteraemia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Biliary tract infection * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Bronchitis * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Bronchopneumonia * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Cellulitis * 1	6/930 (0.65%)	1/465 (0.22%)	0/87 (0.00%)
Diverticulitis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Enterocolitis infectious * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Gastroenteritis * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Herpes zoster * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Infection * 1	0/930 (0.00%)	1/465 (0.22%)	1/87 (1.15%)
Lower respiratory tract infection * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Lung infection * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Pneumonia * 1	20/930 (2.15%)	2/465 (0.43%)	0/87 (0.00%)
Pneumonia bacterial * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pyelonephritis * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Respiratory tract infection * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Septic shock * 1	3/930 (0.32%)	0/465 (0.00%)	1/87 (1.15%)
Sinusitis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Skin infection * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Small intestine gangrene * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Soft tissue infection * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Tracheobronchitis * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Upper respiratory tract infection * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Urinary tract infection * 1	11/930 (1.18%)	6/465 (1.29%)	0/87 (0.00%)
Urosepsis * 1	9/930 (0.97%)	1/465 (0.22%)	0/87 (0.00%)
Viral diarrhoea * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Viral infection * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Sepsis * 1	6/930 (0.65%)	0/465 (0.00%)	0/87 (0.00%)
Pyelonephritis acute * 1	0/930 (0.00%)	2/465 (0.43%)	0/87 (0.00%)
Bacterial sepsis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cystitis * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Device related infection * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Diarrhoea infectious * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Erysipelas * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Lobar pneumonia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Nail bed infection * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Peritonsillar abscess * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Tooth infection * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Injury, poisoning and procedural complications
Ankle fracture * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Clavicle fracture * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Comminuted fracture * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Concussion * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cystitis radiation * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Excoriation * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Fall * 1	12/930 (1.29%)	2/465 (0.43%)	0/87 (0.00%)
Femoral neck fracture * 1	6/930 (0.65%)	0/465 (0.00%)	0/87 (0.00%)
Femur fracture * 1	5/930 (0.54%)	1/465 (0.22%)	0/87 (0.00%)
Fibula fracture * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Forearm fracture * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Fracture * 1	4/930 (0.43%)	0/465 (0.00%)	0/87 (0.00%)
Heat stroke * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Hip fracture * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Humerus fracture * 1	3/930 (0.32%)	1/465 (0.22%)	0/87 (0.00%)
Infusion related reaction * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Lumbar vertebral fracture * 1	3/930 (0.32%)	1/465 (0.22%)	0/87 (0.00%)
Patella fracture * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Pelvic fracture * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Pubis fracture * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Radius fracture * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Rib fracture * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Spinal fracture * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Subdural haematoma * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Tendon rupture * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Tibia fracture * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Ulna fracture * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Upper limb fracture * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Urostomy complication * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Venous injury * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Spinal compression fracture * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Thoracic vertebral fracture * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Cervical vertebral fracture * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Chemical cystitis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Facial bones fracture * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Laceration * 1	0/930 (0.00%)	0/465 (0.00%)	1/87 (1.15%)
Toxicity to various agents * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Investigations
Alanine aminotransferase increased * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Blood creatinine increased * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Blood pressure decreased * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Blood urea increased * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Haemoglobin decreased * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
International normalised ratio increased * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Metabolism and nutrition disorders
Dehydration * 1	4/930 (0.43%)	1/465 (0.22%)	0/87 (0.00%)
Haemochromatosis * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Hyperkalaemia * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Hyponatraemia * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Decreased appetite * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Type 2 diabetes mellitus * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Musculoskeletal and connective tissue disorders
Arthritis * 1	4/930 (0.43%)	0/465 (0.00%)	0/87 (0.00%)
Back pain * 1	1/930 (0.11%)	3/465 (0.65%)	0/87 (0.00%)
Bone pain * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Cervical spinal stenosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Flank pain * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Intervertebral disc protrusion * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Lumbar spinal stenosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Mobility decreased * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Muscular weakness * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Musculoskeletal pain * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Osteoarthritis * 1	5/930 (0.54%)	3/465 (0.65%)	1/87 (1.15%)
Osteonecrosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pathological fracture * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Rheumatoid arthritis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Rotator cuff syndrome * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Spinal column stenosis * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Arthralgia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Osteoporotic fracture * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pain in extremity * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Adenocarcinoma of colon * 1	6/930 (0.65%)	2/465 (0.43%)	0/87 (0.00%)
Basal cell carcinoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Bladder cancer * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Bladder neoplasm * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Bladder papilloma * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Bladder transitional cell carcinoma * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Brain neoplasm * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Chronic lymphocytic leukaemia * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Colon cancer * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Colorectal adenocarcinoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Gastric cancer * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Malignant neoplasm of unknown primary site * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Mesothelioma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Metastases to bone * 1	2/930 (0.22%)	2/465 (0.43%)	0/87 (0.00%)
Metastases to liver * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Metastases to lymph nodes * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Metastases to peritoneum * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Metastases to rectum * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Metastases to spine * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Metastatic neoplasm * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Neoplasm * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Neoplasm progression * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Non-Hodgkin's lymphoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Non-small cell lung cancer * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pancreatic carcinoma metastatic * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Pituitary tumour benign * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Prostate cancer metastatic * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Rectal adenocarcinoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Rectal adenoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Small cell lung cancer * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Small intestine adenocarcinoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Transitional cell carcinoma * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Waldenstrom's macroglobulinaemia * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Prostate cancer * 1	2/930 (0.22%)	1/465 (0.22%)	0/87 (0.00%)
Clear cell renal cell carcinoma * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Squamous cell carcinoma of skin * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Bladder cancer recurrent * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Glioblastoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Hypopharyngeal cancer * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Laryngeal cancer recurrent * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Laryngeal squamous cell carcinoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Lung adenocarcinoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Lung cancer metastatic * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Malignant melanoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Neuroendocrine carcinoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pancreatic carcinoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Nervous system disorders
Carotid artery occlusion * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Carotid artery stenosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cerebral haemorrhage * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Cerebral infarction * 1	4/930 (0.43%)	0/465 (0.00%)	0/87 (0.00%)
Cerebral ischaemia * 1	0/930 (0.00%)	2/465 (0.43%)	0/87 (0.00%)
Cerebrovascular accident * 1	7/930 (0.75%)	1/465 (0.22%)	0/87 (0.00%)
Cognitive disorder * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Convulsion * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Cranial nerve disorder * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Diplegia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Encephalopathy * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Grand mal convulsion * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Ischaemic stroke * 1	6/930 (0.65%)	1/465 (0.22%)	0/87 (0.00%)
Lacunar infarction * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Lethargy * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Loss of consciousness * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Presyncope * 1	3/930 (0.32%)	0/465 (0.00%)	0/87 (0.00%)
Spinal cord compression * 1	3/930 (0.32%)	1/465 (0.22%)	0/87 (0.00%)
Syncope * 1	7/930 (0.75%)	2/465 (0.43%)	1/87 (1.15%)
Transient ischaemic attack * 1	5/930 (0.54%)	1/465 (0.22%)	0/87 (0.00%)
Haemorrhagic stroke * 1	1/930 (0.11%)	0/465 (0.00%)	1/87 (1.15%)
Headache * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Aphasia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Basal ganglia haemorrhage * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Dementia * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Lumbar radiculopathy * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Neuralgia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Sciatica * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Vertigo CNS origin * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Psychiatric disorders
Anxiety * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Depression * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Mania * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Alcohol abuse * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Confusional state * 1	0/930 (0.00%)	0/465 (0.00%)	1/87 (1.15%)
Renal and urinary disorders
Azotaemia * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Bladder disorder * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Bladder hypertrophy * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Bladder obstruction * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Bladder outlet obstruction * 1	1/930 (0.11%)	2/465 (0.43%)	0/87 (0.00%)
Calculus bladder * 1	2/930 (0.22%)	2/465 (0.43%)	0/87 (0.00%)
Calculus ureteric * 1	3/930 (0.32%)	1/465 (0.22%)	0/87 (0.00%)
Cystitis haemorrhagic * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Cystitis noninfective * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Haematuria * 1	31/930 (3.33%)	15/465 (3.23%)	1/87 (1.15%)
Hydronephrosis * 1	5/930 (0.54%)	3/465 (0.65%)	1/87 (1.15%)
Hypertonic bladder * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Nephrolithiasis * 1	5/930 (0.54%)	2/465 (0.43%)	0/87 (0.00%)
Obstructive uropathy * 1	0/930 (0.00%)	3/465 (0.65%)	0/87 (0.00%)
Postrenal failure * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Renal colic * 1	2/930 (0.22%)	2/465 (0.43%)	0/87 (0.00%)
Renal failure * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Renal failure acute * 1	7/930 (0.75%)	8/465 (1.72%)	0/87 (0.00%)
Renal failure chronic * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Renal impairment * 1	1/930 (0.11%)	2/465 (0.43%)	0/87 (0.00%)
Renal pain * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Ureteric obstruction * 1	2/930 (0.22%)	2/465 (0.43%)	1/87 (1.15%)
Ureteric stenosis * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Urethral obstruction * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Urethral stenosis * 1	1/930 (0.11%)	3/465 (0.65%)	0/87 (0.00%)
Urinary fistula * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Urinary incontinence * 1	3/930 (0.32%)	1/465 (0.22%)	0/87 (0.00%)
Urinary retention * 1	13/930 (1.40%)	12/465 (2.58%)	0/87 (0.00%)
Urinary tract obstruction * 1	4/930 (0.43%)	2/465 (0.43%)	0/87 (0.00%)
Vesical fistula * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Anuria * 1	0/930 (0.00%)	0/465 (0.00%)	1/87 (1.15%)
Stress urinary incontinence * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Urinary bladder haemorrhage * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Urinary tract disorder * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Penile pain * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Prostatic cyst * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Prostatic haemorrhage * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Prostatic obstruction * 1	0/930 (0.00%)	1/465 (0.22%)	0/87 (0.00%)
Prostatomegaly * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Prostatitis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Choking * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Chronic obstructive pulmonary disease * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Dyspnoea * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Interstitial lung disease * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Laryngeal oedema * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pleural effusion * 1	4/930 (0.43%)	0/465 (0.00%)	0/87 (0.00%)
Pleurisy * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pneumonia aspiration * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Pulmonary embolism * 1	4/930 (0.43%)	3/465 (0.65%)	0/87 (0.00%)
Epistaxis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Lung disorder * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pneumonitis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Pulmonary oedema * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Surgical and medical procedures
Bladder calculus removal * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Cystoprostatectomy * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Transurethral prostatectomy * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Vascular disorders
Aortic aneurysm * 1	4/930 (0.43%)	0/465 (0.00%)	0/87 (0.00%)
Aortic dissection * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Aortic stenosis * 1	1/930 (0.11%)	1/465 (0.22%)	0/87 (0.00%)
Deep vein thrombosis * 1	1/930 (0.11%)	2/465 (0.43%)	0/87 (0.00%)
Haemorrhage * 1	2/930 (0.22%)	0/465 (0.00%)	0/87 (0.00%)
Hypertension * 1	5/930 (0.54%)	0/465 (0.00%)	0/87 (0.00%)
Ischaemia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Peripheral arterial occlusive disease * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Peripheral artery stenosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Peripheral ischaemia * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Thrombosis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Angiopathy * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Aortic rupture * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Haematoma * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Hypertensive crisis * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
Venous thrombosis limb * 1	1/930 (0.11%)	0/465 (0.00%)	0/87 (0.00%)
1 Term from vocabulary, MedDRA 16.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Enzalutamide 160 mg	Placebo	Placebo Patients Crossover to Enzalutamide 160 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	762/930 (81.94%)	299/465 (64.30%)	45/87 (51.72%)
Blood and lymphatic system disorders
Anaemia * 1	63/930 (6.77%)	20/465 (4.30%)	7/87 (8.05%)
Gastrointestinal disorders
Constipation * 1	121/930 (13.01%)	39/465 (8.39%)	1/87 (1.15%)
Diarrhoea * 1	112/930 (12.04%)	47/465 (10.11%)	3/87 (3.45%)
Nausea * 1	125/930 (13.44%)	42/465 (9.03%)	3/87 (3.45%)
General disorders
Asthenia * 1	94/930 (10.11%)	32/465 (6.88%)	10/87 (11.49%)
Fatigue * 1	348/930 (37.42%)	73/465 (15.70%)	13/87 (14.94%)
Oedema peripheral * 1	59/930 (6.34%)	23/465 (4.95%)	4/87 (4.60%)
Infections and infestations
Urinary tract infection * 1	70/930 (7.53%)	33/465 (7.10%)	1/87 (1.15%)
Injury, poisoning and procedural complications
Fall * 1	164/930 (17.63%)	25/465 (5.38%)	2/87 (2.30%)
Rib fracture * 1	64/930 (6.88%)	7/465 (1.51%)	1/87 (1.15%)
Investigations
Weight decreased * 1	80/930 (8.60%)	11/465 (2.37%)	4/87 (4.60%)
Metabolism and nutrition disorders
Decreased appetite * 1	108/930 (11.61%)	22/465 (4.73%)	3/87 (3.45%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	119/930 (12.80%)	36/465 (7.74%)	3/87 (3.45%)
Back pain * 1	120/930 (12.90%)	38/465 (8.17%)	4/87 (4.60%)
Musculoskeletal pain * 1	61/930 (6.56%)	15/465 (3.23%)	1/87 (1.15%)
Pain in extremity * 1	56/930 (6.02%)	15/465 (3.23%)	2/87 (2.30%)
Nervous system disorders
Dizziness * 1	112/930 (12.04%)	27/465 (5.81%)	6/87 (6.90%)
Headache * 1	103/930 (11.08%)	23/465 (4.95%)	3/87 (3.45%)
Renal and urinary disorders
Haematuria * 1	97/930 (10.43%)	41/465 (8.82%)	2/87 (2.30%)
Urinary retention * 1	43/930 (4.62%)	36/465 (7.74%)	0/87 (0.00%)
Pollakiuria * 1	43/930 (4.62%)	25/465 (5.38%)	0/87 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	48/930 (5.16%)	15/465 (3.23%)	1/87 (1.15%)
Vascular disorders
Hot flush * 1	132/930 (14.19%)	38/465 (8.17%)	3/87 (3.45%)
Hypertension * 1	161/930 (17.31%)	27/465 (5.81%)	6/87 (6.90%)
1 Term from vocabulary, MedDRA 16.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

De Giorgi U, Hussain M, Shore N, Fizazi K, Tombal B, Penson D, Saad F, Efstathiou E, Madziarska K, Steinberg J, Sugg J, Lin X, Shen Q, Sternberg CN. Which traits affect how long patients with advanced prostate cancer live when treated with enzalutamide? Future Oncol. 2022 Nov;18(35):3867-3874. doi: 10.2217/fon-2022-0661. Epub 2022 Oct 13.

Cella D, Ganguli A, Turnbull J, Rohay J, Morlock R. US Population Reference Values for Health-Related Quality of Life Questionnaires Based on Demographics of Patients with Prostate Cancer. Adv Ther. 2022 Aug;39(8):3696-3710. doi: 10.1007/s12325-022-02204-3. Epub 2022 Jun 22.

Joshua AM, Armstrong A, Crumbaker M, Scher HI, de Bono J, Tombal B, Hussain M, Sternberg CN, Gillessen S, Carles J, Fizazi K, Lin P, Duggan W, Sugg J, Russell D, Beer TM. Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER. Eur J Cancer. 2022 Jul;170:285-295. doi: 10.1016/j.ejca.2022.04.005. Epub 2022 May 26.

De Giorgi U, Hussain M, Shore N, Fizazi K, Tombal B, Penson D, Saad F, Efstathiou E, Madziarska K, Steinberg J, Sugg J, Lin X, Shen Q, Sternberg CN. Consistent survival benefit of enzalutamide plus androgen deprivation therapy in men with nonmetastatic castration-resistant prostate cancer: PROSPER subgroup analysis by age and region. Eur J Cancer. 2021 Dec;159:237-246. doi: 10.1016/j.ejca.2021.10.015. Epub 2021 Nov 14.

Saad F, Sternberg CN, Efstathiou E, Fizazi K, Modelska K, Lin X, Sugg J, Steinberg J, Noerby B, Shore ND, Hussain M. Prostate-specific Antigen Progression in Enzalutamide-treated Men with Nonmetastatic Castration-resistant Prostate Cancer: Any Rise in Prostate-specific Antigen May Require Closer Monitoring. Eur Urol. 2020 Dec;78(6):847-853. doi: 10.1016/j.eururo.2020.08.025. Epub 2020 Oct 1.

Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, Ferreira U, Efstathiou E, Madziarska K, Kolinsky MP, Cubero DIG, Noerby B, Zohren F, Lin X, Modelska K, Sugg J, Steinberg J, Hussain M; PROSPER Investigators. Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2197-2206. doi: 10.1056/NEJMoa2003892. Epub 2020 May 29.

Tombal B, Saad F, Penson D, Hussain M, Sternberg CN, Morlock R, Ramaswamy K, Ivanescu C, Attard G. Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 Apr;20(4):556-569. doi: 10.1016/S1470-2045(18)30898-2. Epub 2019 Feb 12.

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, Ivashchenko P, Demirhan E, Modelska K, Phung D, Krivoshik A, Sternberg CN. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474. doi: 10.1056/NEJMoa1800536.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02003924
• Other Study ID Numbers: MDV3100-14; C3431005 ( Other Identifier: Alias Study Number ); 2012-005665-12 ( EudraCT Number )
• First Submitted: December 3, 2013
• First Posted: December 6, 2013
• Results First Submitted: June 15, 2018
• Results First Posted: July 12, 2018
• Last Update Posted: April 23, 2024