A Study of Vemurafenib Adjuvant Therapy in Participants With Surgically Resected Cutaneous BRAF-Mutant Melanoma (BRIM8)

• ClinicalTrials.gov Identifier: NCT01667419
• Recruitment Status: Completed
• First Posted: August 17, 2012
• Results First Posted: October 17, 2018
• Last Update Posted: July 23, 2019
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Melanoma
• Interventions: Drug: Vemurafenib; Drug: Placebo
• Enrollment: 498

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
Arm/Group Description	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 milligrams (mg) twice daily, in 28-day cycles, for up to 52 weeks	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Period Title: Overall Study
Started	157	157	93	91
Completed	114	110	57	52
Not Completed	43	47	36	39
Reason Not Completed
Reason Not Specified	1	0	0	0
Withdrawal by Subject	16	8	9	8
Non-compliance	0	0	0	1
Protocol Violation	1	0	0	0
Lost to Follow-up	7	6	2	4
Death	18	33	25	26

Baseline Characteristics

Arm/Group Title		Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo	Total
Arm/Group Description		Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Total of all reporting groups
Overall Number of Baseline Participants		157	157	93	91	498
Baseline Analysis Population Description		The intent-to-treat (ITT) population included all participants enrolled in the study, whether or not they had received study medication.
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	157 participants	157 participants	93 participants	91 participants	498 participants
		50.7 (12.4)	49.6 (12.7)	51.6 (14.1)	49.1 (12.9)	50.2 (12.9)
		[1] Measure Analysis Population Description: The intent-to-treat (ITT) population included all participants enrolled in the study, whether or not they had received study medication.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	157 participants	157 participants	93 participants	91 participants	498 participants
	Female	73 46.5%	69 43.9%	41 44.1%	32 35.2%	215 43.2%
	Male	84 53.5%	88 56.1%	52 55.9%	59 64.8%	283 56.8%
		[1] Measure Analysis Population Description: The intent-to-treat (ITT) population included all participants enrolled in the study, whether or not they had received study medication.
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	157 participants	157 participants	93 participants	91 participants	498 participants
	Hispanic or Latino	12 7.6%	2 1.3%	8 8.6%	3 3.3%	25 5.0%
	Not Hispanic or Latino	138 87.9%	148 94.3%	79 84.9%	80 87.9%	445 89.4%
	Unknown or Not Reported	7 4.5%	7 4.5%	6 6.5%	8 8.8%	28 5.6%
		[1] Measure Analysis Population Description: The intent-to-treat (ITT) population included all participants enrolled in the study, whether or not they had received study medication.
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	157 participants	157 participants	93 participants	91 participants	498 participants
White		150 95.5%	150 95.5%	84 90.3%	81 89.0%	465 93.4%
Other		1 0.6%	2 1.3%	1 1.1%	2 2.2%	6 1.2%
Multiple		0 0.0%	0 0.0%	1 1.1%	0 0.0%	1 0.2%
Unknown		6 3.8%	5 3.2%	7 7.5%	8 8.8%	26 5.2%
		[1] Measure Analysis Population Description: The intent-to-treat (ITT) population included all participants enrolled in the study, whether or not they had received study medication.

Outcome Measures

1. Primary Outcome

Title	Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)
Description	DFS was defined as the time from randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause.
Time Frame	From randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants enrolled in the study, whether or not they had received study medication.

Arm/Group Title	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
Arm/Group Description:	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Overall Number of Participants Analyzed	157	157	93	91
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	36.9 [1]; (21.4 to NA)	23.1; (18.6 to 26.5)	15.4; (11.1 to 35.9)

[1]

Not estimable due to low number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1 Vemurafenib, Cohort 1 Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0010
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.78
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 2 Vemurafenib, Cohort 2 Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2598
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.18
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Distant Metastasis-Free Survival (DMFS) as Assessed Using Contrast-Enhanced MRI or Contrast Enhanced CT
Description	DMFS was defined as the time from randomization until the date of diagnosis of distant (i.e. non-locoregional) metastases or death from any cause.
Time Frame	From randomization until the date of diagnosis of distant (i.e., non-locoregional) metastases or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants enrolled in the study, whether or not they had received study medication.

Arm/Group Title	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
Arm/Group Description:	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Overall Number of Participants Analyzed	157	157	93	91
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (36.9 to NA)	37.2 [1]; (22.1 to NA)	30.7 [1]; (24.5 to NA)

[1]

Not estimable due to low number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1 Vemurafenib, Cohort 1 Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0133
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.90
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 2 Vemurafenib, Cohort 2 Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6815
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.44
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from randomization until the date of death from any cause.
Time Frame	From randomization until the date of death from any cause (up until 13-July-2018, approximately 6 years)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants enrolled in the study, whether or not they had received study medication.

Arm/Group Title	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
Arm/Group Description:	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Overall Number of Participants Analyzed	157	157	93	91
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (60 to NA)	NA [1]; (NA to NA)	59.9; (54.6 to 59.9)	NA [1]; (52.6 to NA)

[1]

Not estimable due to low number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort 1 Vemurafenib, Cohort 1 Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0274
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.30 to .94
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort 2 Vemurafenib, Cohort 2 Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8597
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.95
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.66
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
Time Frame	From randomization up to study completion or discontinuation (up until 13-July-2018, approximately 6 years)

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of study medication.

Arm/Group Title	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
Arm/Group Description:	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Overall Number of Participants Analyzed	154	156	93	91
Measure Type: Number; Unit of Measure: percentage of participants
	99.4	88.5	100.0	89.0

5. Secondary Outcome

Title	Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Score
Description	European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire assesses 8 symptoms, function, financial difficulties, and a global health status/health-related quality of life (HRQoL). Most questions use a 4-point scale (1 'Not at all' to 4 'Very much';2 questions use a 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. Higher scores for the function and HRQoL represent higher levels of functioning and HRQoL, higher scores for the symptom represent higher levels of symptoms/problems, higher score for financial difficulty represent higher level of perceived financial burden of treatment. Changes of 5-10 points are considered to represent a minimally important difference to participants. A positive value means an increase, and negative value means a decrease in score at the indicated time-point relative to the score at baseline (Cycle 1 Day 1).
Time Frame	Day 1, Day 8, Day 15, Day 22 of Cycle 1;Day 1, Day 15 of Cycle 2;Day 1 Cycles 3-13;end of treatment(up to 13 months);every 13 weeks thereafter until recurrence or occurrence of a new primary melanoma (up to 17-Apr-17 data cut-off,approximately 4.5 years)

Outcome Measure Data

Analysis Population Description

The patient-reported outcome (PRO)-evaluable population included all participants who received at least one dose of vemurafenib and who had both a baseline assessment and at least one post-baseline QLQ-C30 assessment that generated a score.

Arm/Group Title		Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
Arm/Group Description:		Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
Overall Number of Participants Analyzed		138	147	87	89
Mean (Standard Deviation); Unit of Measure: score on a scale
Appetite Loss: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	86 participants	89 participants
		3.6 (11.2)	3.9 (14.9)	3.5 (10.3)	3.4 (11.3)
Appetite Loss: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		2.8 (9.4)	1.5 (7.1)	10.4 (16.0)	0.0 (11.1)
Appetite Loss: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	79 participants	84 participants
		16.7 (26.5)	1.4 (12.0)	12.2 (22.8)	1.2 (17.5)
Appetite Loss: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		7.6 (14.3)	3.2 (10.0)	11.1 (20.6)	3.9 (20.0)
Appetite Loss: Change at Cycle 2 Day 1	Number Analyzed	126 participants	142 participants	82 participants	84 participants
		9.5 (21.0)	1.2 (10.1)	12.2 (23.7)	1.6 (15.4)
Appetite Loss: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	79 participants	81 participants
		9.5 (22.2)	1.0 (12.2)	6.8 (16.3)	0.8 (14.9)
Appetite Loss: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	80 participants	77 participants
		10.4 (20.7)	1.6 (10.1)	8.3 (18.0)	0.4 (14.8)
Appetite Loss: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		9.5 (20.9)	1.3 (12.1)	10.3 (20.3)	2.6 (15.2)
Appetite Loss: Change at Cycle 5 Day 1	Number Analyzed	110 participants	117 participants	72 participants	64 participants
		13.3 (23.5)	1.4 (12.7)	7.4 (15.0)	-0.5 (12.6)
Appetite Loss: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		9.7 (21.1)	2.4 (12.4)	13.0 (21.6)	1.1 (17.9)
Appetite Loss: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		10.7 (22.8)	1.5 (14.0)	7.4 (16.1)	4.0 (18.7)
Appetite Loss: Change at Cycle 8 Day 1	Number Analyzed	105 participants	105 participants	65 participants	53 participants
		10.2 (22.7)	1.9 (13.7)	10.8 (18.7)	-0.6 (12.2)
Appetite Loss: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		9.7 (25.2)	2.3 (13.5)	7.9 (17.7)	3.8 (15.7)
Appetite Loss: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		7.3 (18.9)	1.7 (15.5)	4.8 (15.7)	0.0 (12.0)
Appetite Loss: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		5.4 (19.2)	1.8 (14.2)	4.7 (13.3)	0.7 (12.8)
Appetite Loss: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		8.5 (20.9)	1.5 (14.0)	7.3 (15.3)	0.0 (11.9)
Appetite Loss: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		5.7 (17.2)	1.9 (13.6)	6.2 (14.6)	0.7 (11.2)
Appetite Loss: Change at End of Treatment	Number Analyzed	123 participants	125 participants	66 participants	75 participants
		2.7 (16.3)	0.8 (20.1)	5.1 (18.7)	2.7 (18.8)
Appetite Loss: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	55 participants	38 participants
		0.0 (13.2)	1.8 (16.5)	-1.2 (6.3)	1.8 (10.8)
Appetite Loss: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		0.7 (16.6)	-1.4 (15.3)	3.5 (17.4)	1.0 (12.7)
Appetite Loss: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	42 participants	33 participants
		-0.4 (12.5)	-0.5 (7.0)	-0.8 (9.0)	2.0 (14.3)
Appetite Loss: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	26 participants	25 participants
		0.4 (17.6)	0.0 (12.1)	-1.3 (6.5)	2.7 (9.2)
Appetite Loss: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		-1.9 (12.1)	0.9 (14.5)	0.0 (0.0)	5.6 (17.1)
Appetite Loss: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		-0.7 (11.1)	2.0 (14.3)	0.0 (0.0)	3.7 (11.1)
Appetite Loss: Change at PT 91 Weeks	Number Analyzed	32 participants	29 participants	15 participants	12 participants
		2.1 (16.8)	2.3 (12.4)	0.0 (0.0)	2.8 (9.6)
Appetite Loss: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		-1.2 (11.3)	-1.3 (6.7)	0.0 (0.0)	-3.7 (11.1)
Appetite Loss: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	9 participants	5 participants
		-1.5 (12.5)	2.0 (14.3)	0.0 (0.0)	0.0 (0.0)
Appetite Loss: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		0.0 (0.0)	2.8 (17.2)	0.0 (0.0)	0.0 (0.0)
Appetite Loss: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		-4.8 (12.6)	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)
Appetite Loss: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		0.0 (0.0)	0.0 [1] (NA)		16.7 (23.6)
Appetite Loss: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		0.0 (0.0)	0.0 [1] (NA)
Appetite Loss: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		0.0 (0.0)
Appetite Loss: Change at PT/Discontinuation	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		0.0 (0.0)	0.0 [1] (NA)	0.0 (0.0)	0.0 [1] (NA)
Cognitive Functioning: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		93.0 (14.1)	92.0 (16.2)	91.4 (17.2)	94.9 (11.6)
Cognitive Functioning: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		-2.1 (12.3)	1.5 (14.5)	0.0 (10.5)	2.6 (6.2)
Cognitive Functioning: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	78 participants	84 participants
		-4.3 (13.1)	0.8 (12.6)	-3.8 (13.4)	-0.8 (11.5)
Cognitive Functioning: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		-0.8 (17.4)	1.6 (11.7)	-3.3 (9.3)	-4.9 (14.1)
Cognitive Functioning: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	82 participants	84 participants
		-2.4 (14.2)	-2.5 (14.3)	-2.2 (12.2)	0.0 (13.9)
Cognitive Functioning: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	80 participants
		-3.8 (15.1)	-1.1 (14.6)	-3.1 (11.9)	-0.4 (15.2)
Cognitive Functioning: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		-3.6 (13.4)	-0.6 (12.0)	-2.5 (12.4)	-2.1 (13.3)
Cognitive Functioning: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		-3.8 (14.6)	-1.3 (15.1)	-4.9 (13.5)	-2.9 (13.7)
Cognitive Functioning: Change at Cycle 5 Day 1	Number Analyzed	110 participants	116 participants	72 participants	64 participants
		-6.2 (17.3)	-2.0 (14.9)	-3.9 (12.7)	-3.6 (15.3)
Cognitive Functioning: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		-5.7 (15.8)	-2.1 (12.5)	-4.1 (16.0)	-3.4 (18.2)
Cognitive Functioning: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		-6.3 (17.3)	-3.1 (13.3)	-3.9 (15.5)	-5.6 (15.0)
Cognitive Functioning: Change at Cycle 8 Day 1	Number Analyzed	104 participants	106 participants	65 participants	53 participants
		-7.4 (16.1)	-3.6 (16.9)	-5.1 (16.6)	-4.7 (13.2)
Cognitive Functioning: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		-8.2 (18.1)	-4.6 (17.3)	-5.8 (17.7)	-5.4 (12.2)
Cognitive Functioning: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		-9.0 (20.1)	-3.6 (17.4)	-4.5 (17.5)	-8.2 (19.3)
Cognitive Functioning: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		-10.6 (20.1)	-2.9 (15.9)	-5.0 (15.1)	-3.8 (12.5)
Cognitive Functioning: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		-8.7 (21.5)	-4.0 (14.6)	-3.9 (13.6)	-4.5 (14.5)
Cognitive Functioning: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		-7.7 (20.7)	-3.9 (16.1)	-6.5 (15.7)	-5.2 (12.7)
Cognitive Functioning: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		-4.9 (17.3)	-3.5 (19.5)	-4.0 (17.2)	-6.9 (14.3)
Cognitive Functioning: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		-4.4 (14.9)	-1.6 (14.1)	-1.5 (14.0)	-3.5 (14.1)
Cognitive Functioning: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		-2.8 (16.2)	-2.5 (14.2)	-2.1 (15.4)	-3.8 (13.5)
Cognitive Functioning: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	41 participants	33 participants
		-2.1 (13.2)	-1.0 (14.6)	-2.0 (11.9)	-3.0 (11.4)
Cognitive Functioning: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		-3.5 (17.3)	-1.9 (9.1)	1.2 (13.0)	-7.3 (12.8)
Cognitive Functioning: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		-4.4 (17.3)	-3.9 (15.2)	-1.0 (12.5)	-4.6 (11.2)
Cognitive Functioning: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		-2.5 (17.2)	-3.5 (19.4)	-1.1 (14.7)	-7.4 (12.1)
Cognitive Functioning: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		-2.5 (16.2)	-2.3 (15.9)	3.3 (11.3)	-5.6 (13.0)
Cognitive Functioning: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		1.2 (14.6)	-4.0 (16.9)	3.3 (13.1)	-5.6 (11.8)
Cognitive Functioning: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	8 participants	5 participants
		1.5 (12.5)	0.0 (10.2)	-2.1 (5.9)	-6.7 (14.9)
Cognitive Functioning: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		-3.9 (15.1)	-1.4 (15.0)	0.0 (0.0)	-6.7 (14.9)
Cognitive Functioning: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		4.8 (18.5)	0.0 (0.0)	0.0 (0.0)	-8.3 (11.8)
Cognitive Functioning: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		11.1 (19.2)	0.0 [1] (NA)		-16.7 (23.6)
Cognitive Functioning: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		16.7 (23.6)	0.0 [1] (NA)
Cognitive Functioning: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		11.1 (19.2)
Cognitive Functioning: Change at PT/Discontin.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		-2.1 (16.5)	0.0 [1] (NA)	-5.6 (8.6)	0.0 [1] (NA)
Constipation: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	146 participants	87 participants	88 participants
		3.1 (10.6)	5.7 (16.3)	4.6 (12.6)	5.7 (15.3)
Constipation: Change at Cycle 1 Day 8	Number Analyzed	23 participants	22 participants	16 participants	19 participants
		-2.9 (13.9)	0.0 (0.0)	-2.1 (8.3)	-5.3 (12.5)
Constipation: Change at Cycle 1 Day 15	Number Analyzed	130 participants	138 participants	80 participants	83 participants
		2.1 (17.0)	0.7 (13.0)	1.7 (13.9)	-0.4 (16.9)
Constipation: Change at Cycle 1 Day 22	Number Analyzed	21 participants	21 participants	15 participants	17 participants
		-1.6 (19.7)	1.6 (7.3)	0.0 (12.6)	-3.9 (16.2)
Constipation: Change at Cycle 2 Day 1	Number Analyzed	124 participants	141 participants	82 participants	83 participants
		1.1 (12.7)	1.4 (10.4)	1.6 (13.8)	-0.4 (16.9)
Constipation: Change at Cycle 2 Day 15	Number Analyzed	117 participants	133 participants	79 participants	79 participants
		1.4 (14.8)	0.0 (13.0)	0.0 (11.9)	-1.3 (15.5)
Constipation: Change at Cycle 3 Day 1	Number Analyzed	115 participants	127 participants	79 participants	77 participants
		-1.2 (12.4)	1.0 (13.9)	0.4 (12.5)	-1.7 (18.7)
Constipation: Change at Cycle 4 Day 1	Number Analyzed	118 participants	127 participants	78 participants	75 participants
		0.6 (11.5)	0.5 (16.8)	0.0 (10.7)	-2.2 (14.8)
Constipation: Change at Cycle 5 Day 1	Number Analyzed	107 participants	116 participants	71 participants	64 participants
		-0.6 (9.1)	0.3 (16.7)	3.8 (14.4)	-3.1 (17.5)
Constipation: Change at Cycle 6 Day 1	Number Analyzed	104 participants	112 participants	68 participants	63 participants
		0.6 (13.1)	1.8 (16.6)	5.4 (16.9)	-3.7 (20.0)
Constipation: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	67 participants	59 participants
		3.1 (18.1)	1.5 (19.0)	3.0 (12.6)	-4.0 (15.3)
Constipation: Change at Cycle 8 Day 1	Number Analyzed	103 participants	106 participants	64 participants	53 participants
		1.9 (14.6)	1.6 (16.2)	4.2 (15.1)	-1.9 (17.8)
Constipation: Change at Cycle 9 Day 1	Number Analyzed	97 participants	101 participants	62 participants	52 participants
		1.4 (11.7)	-2.3 (13.5)	3.2 (14.4)	-0.6 (20.3)
Constipation: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	62 participants	47 participants
		1.4 (10.7)	-1.4 (12.7)	1.6 (11.2)	-4.3 (17.9)
Constipation: Change at Cycle 11 Day 1	Number Analyzed	92 participants	93 participants	56 participants	48 participants
		2.2 (14.7)	0.0 (16.3)	2.4 (14.0)	-4.9 (15.4)
Constipation: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	54 participants	48 participants
		4.8 (19.1)	-1.8 (14.4)	3.1 (13.4)	-3.5 (14.2)
Constipation: Change at Cycle 13 Day 1	Number Analyzed	81 participants	89 participants	54 participants	45 participants
		4.1 (18.5)	0.0 (18.8)	0.0 (11.2)	-3.7 (19.1)
Constipation: Change at End of Treatment	Number Analyzed	122 participants	124 participants	67 participants	74 participants
		3.3 (15.1)	2.4 (19.1)	4.5 (17.3)	-1.4 (17.8)
Constipation: Change at PT 13 Weeks	Number Analyzed	88 participants	74 participants	56 participants	38 participants
		0.4 (17.1)	-0.5 (17.0)	6.0 (16.9)	0.9 (21.2)
Constipation: Change at PT 26 Weeks	Number Analyzed	89 participants	71 participants	47 participants	35 participants
		-0.4 (13.8)	-0.9 (13.8)	2.8 (9.4)	-1.0 (18.9)
Constipation: Change at PT 39 Weeks	Number Analyzed	77 participants	67 participants	41 participants	33 participants
		0.4 (14.8)	-0.5 (13.6)	2.4 (13.7)	-4.0 (16.2)
Constipation: Change at PT 52 Weeks	Number Analyzed	75 participants	62 participants	27 participants	25 participants
		0.0 (13.4)	0.0 (14.8)	0.0 (9.2)	0.0 (13.6)
Constipation: Change at PT 65 Weeks	Number Analyzed	53 participants	37 participants	17 participants	18 participants
		3.8 (14.1)	3.6 (21.9)	2.0 (14.3)	0.0 (11.4)
Constipation: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		-1.4 (9.8)	6.1 (25.6)	0.0 (0.0)	0.0 (0.0)
Constipation: Change at PT 91 Weeks	Number Analyzed	31 participants	28 participants	15 participants	12 participants
		-4.3 (11.4)	6.0 (18.3)	2.2 (8.6)	0.0 (14.2)
Constipation: Change at PT 104 Weeks	Number Analyzed	26 participants	25 participants	10 participants	9 participants
		1.3 (14.8)	4.0 (14.7)	-3.3 (10.5)	0.0 (16.7)
Constipation: Change at PT 117 Weeks	Number Analyzed	20 participants	17 participants	9 participants	5 participants
		-6.7 (13.7)	9.8 (19.6)	0.0 (0.0)	-6.7 (14.9)
Constipation: Change at PT 130 Weeks	Number Analyzed	16 participants	12 participants	5 participants	5 participants
		-8.3 (14.9)	5.6 (13.0)	0.0 (23.6)	-6.7 (14.9)
Constipation: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		-9.5 (16.3)	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)
Constipation: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		0.0 (0.0)	0.0 [1] (NA)		-16.7 (23.6)
Constipation: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		0.0 (0.0)	0.0 [1] (NA)
Constipation: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		-11.1 (19.2)
Constipation: Change at PT/Discontinuation	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		0.0 (0.0)	0.0 [1] (NA)	0.0 (0.0)	0.0 [1] (NA)
Diarrhoea: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		4.1 (13.0)	5.4 (17.5)	3.8 (13.9)	4.1 (16.5)
Diarrhoea: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		4.2 (11.3)	0.0 (10.3)	-4.2 (20.6)	-8.8 (24.4)
Diarrhoea: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	77 participants	84 participants
		2.5 (21.3)	-0.7 (14.7)	1.7 (19.4)	-1.6 (17.1)
Diarrhoea: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		3.0 (9.8)	-1.6 (16.6)	-2.2 (23.5)	-9.8 (25.7)
Diarrhoea: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	82 participants	84 participants
		1.3 (19.9)	-0.9 (16.3)	4.9 (21.7)	0.0 (20.0)
Diarrhoea: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	80 participants
		1.7 (21.2)	-1.5 (19.1)	0.4 (17.2)	0.0 (16.8)
Diarrhoea: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		3.4 (21.9)	-0.3 (18.4)	3.3 (19.4)	-0.9 (15.2)
Diarrhoea: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		3.9 (23.0)	0.3 (19.8)	5.6 (18.2)	-2.6 (18.7)
Diarrhoea: Change at Cycle 5 Day 1	Number Analyzed	110 participants	116 participants	72 participants	64 participants
		7.6 (23.7)	-1.4 (20.3)	2.8 (20.0)	-3.6 (18.9)
Diarrhoea: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		7.2 (25.2)	-0.6 (20.0)	7.2 (24.8)	-2.6 (19.2)
Diarrhoea: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		9.4 (24.2)	-1.5 (21.6)	4.9 (22.5)	-4.5 (18.0)
Diarrhoea: Change at Cycle 8 Day 1	Number Analyzed	104 participants	106 participants	65 participants	52 participants
		5.1 (19.6)	-0.9 (21.3)	5.6 (20.9)	-3.2 (16.5)
Diarrhoea: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	62 participants	52 participants
		7.7 (25.0)	0.7 (24.5)	4.3 (19.5)	-1.9 (23.3)
Diarrhoea: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	62 participants	47 participants
		6.9 (21.6)	-0.3 (22.3)	5.9 (23.8)	-2.1 (18.9)
Diarrhoea: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		6.1 (19.6)	1.1 (23.3)	4.7 (23.1)	-0.7 (20.0)
Diarrhoea: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	47 participants
		7.4 (25.4)	-0.7 (23.3)	7.9 (24.8)	-0.7 (19.0)
Diarrhoea: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		8.5 (24.5)	0.4 (25.4)	8.0 (28.9)	-1.5 (20.0)
Diarrhoea: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		0.8 (21.5)	0.0 (20.7)	-1.0 (16.4)	-1.8 (18.9)
Diarrhoea: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		-0.4 (15.4)	-1.8 (24.0)	0.0 (18.0)	0.0 (15.5)
Diarrhoea: Change at PT 26 Weeks	Number Analyzed	89 participants	72 participants	47 participants	35 participants
		-2.2 (16.5)	-3.2 (24.5)	0.7 (8.5)	-1.9 (19.7)
Diarrhoea: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	41 participants	33 participants
		-1.7 (15.9)	-4.9 (23.2)	1.6 (14.8)	0.0 (18.6)
Diarrhoea: Change at PT 52 Weeks	Number Analyzed	75 participants	62 participants	27 participants	25 participants
		-1.8 (17.2)	-3.8 (23.5)	-1.2 (21.6)	0.0 (19.2)
Diarrhoea: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		0.0 (19.6)	-6.1 (29.9)	2.0 (8.1)	-7.4 (24.4)
Diarrhoea: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		-0.7 (20.5)	-7.1 (29.8)	0.0 (0.0)	-3.7 (11.1)
Diarrhoea: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		4.0 (16.2)	-9.2 (25.0)	0.0 (0.0)	-8.3 (28.9)
Diarrhoea: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		0.0 (9.2)	-5.3 (28.3)	3.3 (10.5)	-11.1 (33.3)
Diarrhoea: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	8 participants	5 participants
		0.0 (10.3)	-11.8 (31.0)	0.0 (0.0)	0.0 (0.0)
Diarrhoea: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		-2.0 (8.1)	-2.8 (43.7)	6.7 (14.9)	13.3 (18.3)
Diarrhoea: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		0.0 (0.0)	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)
Diarrhoea: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		0.0 (0.0)	0.0 [1] (NA)		0.0 (0.0)
Diarrhoea: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		0.0 (0.0)	0.0 [1] (NA)
Diarrhoea: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		0.0 (0.0)
Diarrhoea: Change at PT/Discontinuation	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		0.0 (17.8)	-33.3 [1] (NA)	0.0 (0.0)	0.0 [1] (NA)
Dyspnoea: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		3.6 (10.4)	4.8 (12.9)	5.0 (12.0)	3.0 (10.8)
Dyspnoea: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		4.2 (11.3)	-1.5 (7.1)	4.2 (16.7)	-1.8 (7.6)
Dyspnoea: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	80 participants	84 participants
		6.3 (18.9)	0.2 (8.5)	2.9 (15.2)	1.2 (12.1)
Dyspnoea: Change at Cycle 1 Day 22	Number Analyzed	21 participants	21 participants	15 participants	17 participants
		4.8 (12.0)	-1.6 (7.3)	0.0 (17.8)	0.0 (0.0)
Dyspnoea: Change at Cycle 2 Day 1	Number Analyzed	126 participants	142 participants	83 participants	84 participants
		1.9 (13.5)	0.2 (11.6)	4.8 (20.9)	3.2 (14.3)
Dyspnoea: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	81 participants
		2.8 (16.0)	1.0 (13.5)	4.6 (18.9)	4.1 (17.0)
Dyspnoea: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		3.4 (17.0)	1.8 (13.4)	3.7 (18.3)	3.8 (12.0)
Dyspnoea: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		3.1 (15.6)	3.1 (14.7)	3.0 (18.8)	1.8 (14.3)
Dyspnoea: Change at Cycle 5 Day 1	Number Analyzed	110 participants	116 participants	72 participants	64 participants
		5.2 (14.4)	4.0 (14.7)	3.7 (19.0)	3.1 (15.4)
Dyspnoea: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		3.8 (16.8)	2.4 (13.9)	3.9 (19.4)	2.1 (15.7)
Dyspnoea: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		5.3 (16.7)	3.7 (17.3)	3.9 (17.8)	2.8 (12.8)
Dyspnoea: Change at Cycle 8 Day 1	Number Analyzed	104 participants	106 participants	65 participants	53 participants
		4.2 (16.5)	4.1 (17.6)	2.6 (14.8)	3.1 (13.5)
Dyspnoea: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		5.7 (17.1)	5.3 (16.8)	2.1 (16.8)	4.5 (18.7)
Dyspnoea: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		5.2 (20.1)	4.5 (16.4)	6.3 (18.8)	3.5 (12.5)
Dyspnoea: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		5.7 (19.4)	5.0 (19.0)	7.0 (20.6)	3.5 (14.2)
Dyspnoea: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		6.7 (24.1)	5.5 (18.1)	3.6 (18.9)	5.6 (15.9)
Dyspnoea: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		6.5 (19.2)	4.9 (15.5)	4.9 (19.9)	5.9 (14.7)
Dyspnoea: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		4.1 (14.5)	2.4 (19.9)	3.0 (18.1)	6.2 (16.2)
Dyspnoea: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	55 participants	38 participants
		3.0 (17.1)	3.2 (16.7)	3.0 (16.1)	2.6 (12.0)
Dyspnoea: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		4.8 (16.2)	1.4 (16.3)	3.5 (19.9)	-1.0 (5.6)
Dyspnoea: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	42 participants	33 participants
		1.7 (14.0)	2.5 (13.3)	4.8 (18.9)	3.0 (12.8)
Dyspnoea: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		1.8 (15.3)	3.8 (16.1)	2.5 (15.8)	5.3 (15.8)
Dyspnoea: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		3.8 (14.1)	6.1 (15.2)	-3.9 (11.1)	1.9 (7.9)
Dyspnoea: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		4.3 (13.3)	7.1 (18.2)	0.0 (21.8)	0.0 (16.7)
Dyspnoea: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		3.0 (9.7)	5.7 (12.8)	-2.2 (15.3)	0.0 (14.2)
Dyspnoea: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	8 participants
		0.0 (16.0)	6.7 (16.7)	0.0 (22.2)	8.3 (15.4)
Dyspnoea: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	9 participants	5 participants
		0.0 (14.5)	5.9 (13.1)	-3.7 (20.0)	6.7 (14.9)
Dyspnoea: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		-2.0 (8.1)	0.0 (0.0)	0.0 (23.6)	13.3 (18.3)
Dyspnoea: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		9.5 (25.2)	0.0 (0.0)	-11.1 (19.2)	0.0 (0.0)
Dyspnoea: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		0.0 (0.0)	0.0 [1] (NA)		16.7 (23.6)
Dyspnoea: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		0.0 (0.0)	0.0 [1] (NA)
Dyspnoea: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		0.0 (0.0)
Dyspnoea: Change at PT/Discontinuation	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		0.0 (0.0)	0.0 [1] (NA)	0.0 (0.0)	0.0 [2] (NA)
Emotional functioning: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		83.8 (15.1)	86.1 (16.4)	81.6 (21.5)	84.5 (17.4)
Emotional functioning: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		-4.5 (15.5)	1.9 (12.0)	3.6 (11.4)	1.8 (14.0)
Emotional functioning: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	78 participants	84 participants
		-5.2 (18.0)	1.9 (12.3)	-1.0 (16.6)	3.8 (12.0)
Emotional functioning: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		-6.4 (20.6)	2.4 (9.9)	-0.6 (12.8)	-0.5 (17.3)
Emotional functioning: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	82 participants	84 participants
		-1.2 (16.0)	2.5 (13.2)	-1.0 (17.5)	4.0 (12.7)
Emotional functioning: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	80 participants
		0.2 (18.7)	2.0 (15.4)	-0.5 (11.7)	3.8 (13.6)
Emotional functioning: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		-0.1 (17.3)	2.3 (13.2)	-0.8 (16.8)	3.5 (13.9)
Emotional functioning: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		-2.7 (18.9)	1.8 (15.1)	-1.2 (15.9)	2.4 (14.9)
Emotional functioning: Change at Cycle 5 Day 1	Number Analyzed	110 participants	116 participants	72 participants	64 participants
		-3.5 (19.8)	-0.2 (18.4)	-0.8 (15.4)	3.0 (14.4)
Emotional functioning: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		-2.8 (17.5)	-0.7 (16.7)	-2.6 (16.0)	1.4 (18.7)
Emotional functioning: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		-3.0 (18.5)	0.5 (16.4)	-2.3 (16.1)	-0.5 (14.4)
Emotional functioning: Change at Cycle 8 Day 1	Number Analyzed	104 participants	106 participants	65 participants	53 participants
		-3.5 (20.0)	-0.9 (15.5)	-1.9 (15.9)	0.2 (13.1)
Emotional functioning: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		-1.6 (22.1)	-0.9 (17.0)	0.1 (15.8)	-0.2 (16.1)
Emotional functioning: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		-1.0 (20.5)	-1.1 (14.3)	-0.1 (16.5)	0.0 (14.6)
Emotional functioning: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		0.0 (19.6)	0.5 (14.1)	1.2 (15.7)	0.7 (14.3)
Emotional functioning: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		-2.3 (20.0)	-2.2 (16.4)	1.1 (14.6)	-1.6 (14.1)
Emotional functioning: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		-2.0 (20.4)	-2.5 (18.6)	0.2 (16.5)	0.2 (13.5)
Emotional functioning: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		1.5 (18.8)	-2.0 (19.6)	2.2 (22.2)	-4.4 (19.9)
Emotional functioning: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		3.2 (17.4)	-1.0 (19.5)	6.4 (16.7)	3.5 (13.8)
Emotional functioning: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		4.9 (18.3)	-1.4 (14.1)	3.0 (18.2)	1.2 (16.2)
Emotional functioning: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	41 participants	33 participants
		2.5 (15.5)	-0.2 (14.9)	4.1 (19.0)	2.3 (12.9)
Emotional functioning: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		2.4 (17.8)	-0.7 (16.3)	9.0 (16.8)	1.7 (14.2)
Emotional functioning: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		1.1 (17.9)	-2.0 (17.5)	10.3 (17.1)	3.7 (16.0)
Emotional functioning: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		2.9 (14.6)	-1.8 (22.1)	8.9 (16.2)	1.9 (10.8)
Emotional functioning: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		1.8 (16.8)	0.0 (17.3)	13.3 (16.6)	-0.7 (20.6)
Emotional functioning: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		6.5 (14.3)	-7.0 (21.9)	4.2 (13.2)	1.9 (20.7)
Emotional functioning: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	8 participants	5 participants
		7.2 (12.7)	-2.9 (14.7)	0.0 (16.7)	3.3 (29.8)
Emotional functioning: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		8.7 (12.8)	-4.9 (15.3)	3.3 (20.1)	1.7 (32.5)
Emotional functioning: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		0.0 (18.0)	-4.2 (5.9)	0.0 (25.0)	-16.7 (23.6)
Emotional functioning: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		22.2 (9.6)	0.0 [2] (NA)		4.2 (53.0)
Emotional functioning: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		25.0 (11.8)	0.0 [1] (NA)
Emotional functioning: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		16.7 (16.7)
Emotional functioning: Change at PT/Discont.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		-5.2 (28.1)	0.0 [1] (NA)	1.4 (11.1)	8.3 [1] (NA)
Fatigue: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		13.2 (14.7)	16.1 (19.4)	15.5 (18.2)	14.7 (18.6)
Fatigue: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		7.9 (19.0)	-0.3 (9.8)	7.6 (13.3)	5.3 (10.1)
Fatigue: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	80 participants	84 participants
		22.6 (26.1)	2.3 (14.2)	18.2 (27.0)	3.4 (13.1)
Fatigue: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		15.2 (21.3)	-1.9 (14.4)	17.0 (21.4)	9.2 (15.8)
Fatigue: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	83 participants	84 participants
		13.2 (22.0)	2.5 (15.2)	13.7 (24.2)	2.5 (14.5)
Fatigue: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	81 participants
		15.2 (23.5)	1.5 (18.2)	10.7 (19.9)	2.1 (16.5)
Fatigue: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		14.1 (22.5)	1.5 (16.4)	12.6 (23.1)	4.7 (15.9)
Fatigue: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		12.6 (21.7)	2.0 (18.4)	13.3 (23.1)	3.2 (18.1)
Fatigue: Change at Cycle 5 Day 1	Number Analyzed	110 participants	117 participants	72 participants	64 participants
		14.2 (23.7)	1.9 (16.1)	13.6 (18.9)	4.7 (17.2)
Fatigue: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		11.9 (21.6)	1.5 (17.4)	13.8 (22.2)	3.0 (18.7)
Fatigue: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		13.1 (21.0)	0.2 (18.3)	13.2 (23.2)	6.0 (17.7)
Fatigue: Change at Cycle 8 Day 1	Number Analyzed	105 participants	106 participants	65 participants	53 participants
		14.1 (23.9)	3.9 (21.9)	12.7 (22.7)	5.0 (15.5)
Fatigue: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		16.3 (25.3)	2.7 (20.5)	13.7 (24.1)	6.0 (21.3)
Fatigue: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		11.3 (22.6)	3.4 (18.7)	11.3 (25.0)	3.3 (16.2)
Fatigue: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		11.5 (22.7)	2.7 (18.2)	10.7 (20.9)	7.6 (18.4)
Fatigue: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		10.3 (23.8)	2.1 (16.2)	10.7 (22.5)	3.2 (17.0)
Fatigue: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		11.1 (23.1)	4.0 (19.0)	13.4 (26.6)	4.7 (15.6)
Fatigue: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		6.5 (21.3)	2.2 (24.2)	3.3 (21.9)	6.4 (20.9)
Fatigue: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		1.6 (18.4)	0.7 (19.8)	-1.2 (19.0)	1.5 (14.9)
Fatigue: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		2.5 (18.4)	1.0 (15.5)	0.5 (21.6)	-1.3 (18.8)
Fatigue: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	42 participants	33 participants
		-1.0 (16.9)	0.7 (17.2)	-0.5 (18.2)	-0.3 (12.6)
Fatigue: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		1.6 (16.7)	1.7 (17.6)	-1.2 (14.6)	1.3 (20.6)
Fatigue: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		1.3 (16.5)	4.4 (18.5)	-4.6 (11.8)	-1.2 (17.8)
Fatigue: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		2.4 (16.2)	4.7 (20.8)	-4.4 (10.1)	-4.9 (18.5)
Fatigue: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		-0.8 (16.3)	3.8 (18.8)	-3.7 (15.5)	-2.8 (26.0)
Fatigue: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		-1.2 (14.6)	8.9 (18.7)	-1.1 (17.7)	-1.2 (29.1)
Fatigue: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	9 participants	5 participants
		-3.0 (13.4)	4.2 (19.2)	-7.4 (15.7)	0.0 (28.3)
Fatigue: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		-0.7 (15.5)	6.5 (19.2)	-4.4 (16.9)	0.0 (33.3)
Fatigue: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		-1.6 (14.9)	5.6 (7.9)	-3.7 (17.0)	16.7 (23.6)
Fatigue: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		-11.1 (11.1)	0.0 [1] (NA)		33.3 (15.7)
Fatigue: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		-16.7 (7.9)	0.0 [1] (NA)
Fatigue: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		-14.8 (6.4)
Fatigue: Change at PT/Discontinuation	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		6.9 (16.7)	-22.2 [1] (NA)	-11.1 (25.3)	0.0 [1] (NA)
Financial difficulties: Cycle 1 Day 1 (Baseline)	Number Analyzed	137 participants	147 participants	87 participants	88 participants
		12.4 (25.2)	20.9 (30.0)	16.5 (30.4)	15.9 (26.3)
Financial difficulties: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		-9.7 (25.0)	-3.0 (14.2)	2.1 (8.3)	-7.0 (17.8)
Financial difficulties: Change at Cycle 1 Day 15	Number Analyzed	131 participants	139 participants	78 participants	84 participants
		1.5 (17.5)	-1.9 (20.0)	0.0 (15.2)	-4.4 (21.2)
Financial difficulties: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		-1.5 (26.2)	-3.2 (14.5)	0.0 (0.0)	0.0 (20.4)
Financial difficulties: Change at Cycle 2 Day 1	Number Analyzed	126 participants	141 participants	82 participants	83 participants
		0.0 (17.9)	-3.1 (21.0)	0.8 (16.5)	-4.4 (19.3)
Financial difficulties: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	79 participants
		1.1 (20.8)	-2.2 (20.1)	-0.4 (17.2)	-7.2 (20.4)
Financial difficulties: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	80 participants	77 participants
		0.3 (21.5)	-5.2 (24.1)	1.3 (20.2)	-5.6 (19.8)
Financial difficulties: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	75 participants
		-0.8 (23.6)	-2.8 (24.3)	-0.4 (19.7)	-5.8 (18.5)
Financial difficulties: Change at Cycle 5 Day 1	Number Analyzed	110 participants	116 participants	72 participants	64 participants
		1.2 (23.0)	-5.5 (26.7)	2.3 (18.0)	-7.8 (23.6)
Financial difficulties: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		-0.6 (22.5)	-7.4 (26.4)	2.9 (20.4)	-5.8 (22.0)
Financial difficulties: Change at Cycle 7 Day 1	Number Analyzed	106 participants	107 participants	68 participants	59 participants
		1.9 (26.8)	-5.6 (26.1)	4.9 (27.2)	-5.6 (21.6)
Financial difficulties: Change at Cycle 8 Day 1	Number Analyzed	104 participants	106 participants	65 participants	53 participants
		-0.6 (23.2)	-4.7 (27.0)	4.1 (26.7)	-3.1 (20.9)
Financial difficulties: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		2.0 (24.1)	-8.9 (23.0)	4.2 (23.6)	-5.8 (20.6)
Financial difficulties: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		1.0 (23.4)	-8.6 (25.1)	2.6 (22.6)	-6.4 (20.4)
Financial difficulties: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		1.4 (21.4)	-7.5 (21.5)	0.6 (20.4)	-8.3 (22.3)
Financial difficulties: Change at Cycle 12 Day 1	Number Analyzed	89 participants	90 participants	55 participants	48 participants
		-0.4 (24.4)	-6.3 (23.9)	0.0 (26.4)	-6.3 (23.5)
Financial difficulties: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		1.2 (23.7)	-6.0 (22.2)	-1.9 (27.8)	-8.1 (24.8)
Financial difficulties: Change at End of Treatment	Number Analyzed	122 participants	125 participants	67 participants	75 participants
		2.5 (23.1)	-3.7 (26.5)	-2.5 (23.4)	-0.9 (23.9)
Financial difficulties: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		0.4 (26.2)	-5.9 (24.3)	-10.1 (27.6)	-8.8 (25.3)
Financial difficulties: Change at PT 26 Weeks	Number Analyzed	89 participants	72 participants	47 participants	35 participants
		-3.0 (22.3)	-6.0 (18.8)	-5.7 (26.3)	-7.6 (25.7)
Financial difficulties: Change at PT 39 Weeks	Number Analyzed	78 participants	68 participants	41 participants	33 participants
		-1.7 (22.1)	-7.8 (25.8)	-2.4 (28.3)	-8.1 (26.4)
Financial difficulties: Change at PT 52 Weeks	Number Analyzed	75 participants	62 participants	27 participants	25 participants
		-2.2 (21.5)	-5.4 (21.1)	-11.1 (24.5)	-1.3 (32.6)
Financial difficulties: Change at PT 65 Weeks	Number Analyzed	52 participants	38 participants	17 participants	18 participants
		2.6 (26.3)	-6.1 (30.9)	-9.8 (19.6)	-7.4 (31.4)
Financial difficulties: Change at PT 78 Weeks	Number Analyzed	45 participants	33 participants	15 participants	9 participants
		2.2 (27.9)	-8.1 (31.2)	-11.1 (20.6)	0.0 (16.7)
Financial difficulties: Change at PT 91 Weeks	Number Analyzed	31 participants	29 participants	15 participants	12 participants
		0.0 (27.2)	-10.3 (29.7)	-11.1 (20.6)	-11.1 (32.8)
Financial difficulties: Change at PT 104 Weeks	Number Analyzed	26 participants	25 participants	10 participants	9 participants
		-2.6 (18.7)	-8.0 (30.9)	-13.3 (23.3)	-18.5 (37.7)
Financial difficulties: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	8 participants	5 participants
		-6.1 (22.1)	-5.9 (24.3)	-4.2 (11.8)	-13.3 (18.3)
Financial difficulties: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		-7.8 (27.7)	-5.6 (31.2)	0.0 (0.0)	-20.0 (29.8)
Financial difficulties: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		4.8 (40.5)	16.7 (23.6)	0.0 (0.0)	0.0 (0.0)
Financial difficulties: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		-22.2 (38.5)	0.0 [1] (NA)		-16.7 (23.6)
Financial difficulties: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		0.0 (0.0)	0.0 [1] (NA)
Financial difficulties: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		-22.2 (38.5)
Financial difficulties: Change at PT/Discontin.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		0.0 (17.8)	0.0 [1] (NA)	0.0 (0.0)	0.0 [1] (NA)
Nausea and vomiting: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		1.4 (5.1)	1.8 (9.6)	1.9 (7.4)	1.3 (5.2)
Nausea and vomiting: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		4.2 (8.9)	0.8 (6.3)	5.2 (8.0)	3.5 (8.9)
Nausea and vomiting: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	80 participants	84 participants
		9.8 (16.9)	1.8 (6.9)	8.8 (17.0)	1.2 (7.7)
Nausea and vomiting: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		6.1 (12.1)	0.8 (6.4)	5.6 (10.3)	2.9 (8.8)
Nausea and vomiting: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	83 participants	84 participants
		5.2 (12.9)	0.9 (5.9)	4.6 (11.1)	1.4 (7.9)
Nausea and vomiting: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	81 participants
		6.3 (14.1)	1.1 (8.5)	2.9 (9.1)	1.6 (10.4)
Nausea and vomiting: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		5.7 (13.1)	1.6 (7.3)	4.5 (9.9)	1.3 (8.4)
Nausea and vomiting: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		5.6 (13.6)	1.9 (11.7)	6.6 (14.3)	1.3 (10.8)
Nausea and vomiting: Change at Cycle 5 Day 1	Number Analyzed	110 participants	117 participants	72 participants	64 participants
		7.3 (16.4)	2.6 (9.2)	5.1 (10.7)	-0.5 (7.8)
Nausea and vomiting: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		5.3 (13.1)	2.4 (9.7)	6.3 (12.2)	-0.5 (7.9)
Nausea and vomiting: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		4.7 (11.7)	2.0 (7.8)	4.2 (11.3)	0.6 (6.9)
Nausea and vomiting: Change at Cycle 8 Day 1	Number Analyzed	105 participants	106 participants	65 participants	53 participants
		4.6 (11.9)	1.1 (9.0)	5.9 (15.7)	2.5 (12.4)
Nausea and vomiting: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		5.5 (15.7)	2.5 (10.4)	4.0 (10.2)	0.3 (7.0)
Nausea and vomiting: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		5.2 (13.1)	0.9 (10.3)	4.8 (10.6)	0.4 (6.5)
Nausea and vomiting: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		3.4 (10.9)	2.0 (8.5)	3.2 (8.6)	-0.3 (5.4)
Nausea and vomiting: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		4.3 (12.6)	1.3 (7.9)	4.8 (10.5)	3.5 (13.7)
Nausea and vomiting: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		2.8 (11.7)	1.7 (7.1)	3.4 (9.9)	2.2 (9.8)
Nausea and vomiting: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		0.9 (6.5)	0.3 (12.5)	1.5 (11.9)	3.8 (13.9)
Nausea and vomiting: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		0.2 (6.4)	1.8 (8.5)	0.6 (6.3)	0.9 (6.7)
Nausea and vomiting: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		2.2 (8.7)	0.7 (15.7)	0.7 (10.4)	-1.0 (3.9)
Nausea and vomiting: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	42 participants	33 participants
		0.2 (5.7)	0.2 (6.1)	1.6 (8.1)	1.5 (6.4)
Nausea and vomiting: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		0.9 (6.0)	0.3 (4.8)	0.0 (4.6)	0.7 (3.3)
Nausea and vomiting: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		0.0 (5.7)	3.5 (12.9)	-1.0 (4.0)	2.8 (8.6)
Nausea and vomiting: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		0.4 (5.5)	2.0 (11.6)	-1.1 (4.3)	1.9 (5.6)
Nausea and vomiting: Change at PT 91 Weeks	Number Analyzed	32 participants	29 participants	15 participants	12 participants
		1.6 (6.5)	2.3 (8.6)	-1.1 (4.3)	1.4 (4.8)
Nausea and vomiting: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		1.9 (10.7)	0.0 (4.8)	0.0 (0.0)	0.0 (0.0)
Nausea and vomiting: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	9 participants	5 participants
		-1.5 (4.9)	4.9 (9.8)	-1.9 (5.6)	0.0 (0.0)
Nausea and vomiting: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		0.0 (5.9)	4.2 (10.4)	-3.3 (7.5)	0.0 (0.0)
Nausea and vomiting: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		-2.4 (6.3)	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)
Nausea and vomiting: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		0.0 (0.0)	0.0 [1] (NA)		8.3 (11.8)
Nausea and vomiting: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		0.0 (0.0)	0.0 [1] (NA)
Nausea and vomiting: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		0.0 (0.0)
Nausea and vomiting: Change at PT/Discont.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		4.2 (11.8)	0.0 [1] (NA)	8.3 (13.9)	0.0 [1] (NA)
Pain: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		11.6 (17.5)	12.8 (21.6)	10.9 (19.0)	14.6 (23.9)
Pain: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		9.7 (22.5)	-1.5 (15.4)	10.4 (14.8)	-3.5 (8.9)
Pain: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	80 participants	84 participants
		20.8 (28.5)	0.5 (12.4)	16.3 (28.1)	-1.4 (14.7)
Pain: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		15.9 (28.9)	-3.2 (13.6)	22.2 (18.5)	9.8 (21.3)
Pain: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	83 participants	84 participants
		12.9 (26.5)	0.5 (15.1)	15.1 (28.9)	-3.8 (18.0)
Pain: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	81 participants
		14.3 (27.5)	2.4 (17.2)	12.7 (23.3)	-3.5 (18.0)
Pain: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		11.8 (20.2)	1.2 (16.3)	13.2 (25.6)	-0.6 (17.1)
Pain: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		9.0 (22.1)	4.0 (19.7)	12.0 (25.9)	-2.4 (19.6)
Pain: Change at Cycle 5 Day 1	Number Analyzed	110 participants	117 participants	72 participants	64 participants
		12.7 (24.3)	1.9 (17.6)	14.6 (21.1)	-4.9 (20.5)
Pain: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		8.8 (22.7)	2.2 (18.9)	14.5 (22.9)	-3.7 (20.0)
Pain: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		8.2 (21.4)	0.9 (16.6)	8.3 (20.5)	-2.0 (19.1)
Pain: Change at Cycle 8 Day 1	Number Analyzed	105 participants	106 participants	65 participants	53 participants
		11.0 (24.9)	3.6 (20.1)	12.1 (23.7)	-1.6 (18.3)
Pain: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		12.8 (27.5)	3.6 (21.2)	10.3 (23.5)	-0.3 (23.9)
Pain: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		8.9 (22.0)	1.9 (17.5)	11.6 (24.6)	-3.2 (16.9)
Pain: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		10.0 (25.0)	2.7 (21.3)	13.5 (26.1)	-0.7 (24.3)
Pain: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		12.2 (24.6)	1.3 (19.8)	12.7 (19.5)	-2.1 (20.2)
Pain: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		11.6 (23.5)	3.4 (21.2)	16.4 (27.4)	-1.9 (22.0)
Pain: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		4.9 (23.4)	4.1 (23.3)	6.7 (21.1)	1.6 (21.4)
Pain: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		-0.6 (17.6)	-0.2 (18.2)	4.2 (19.7)	-4.8 (23.5)
Pain: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		1.1 (21.8)	-1.2 (16.6)	7.1 (24.0)	-4.3 (19.5)
Pain: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	42 participants	33 participants
		0.6 (19.9)	2.2 (22.1)	7.5 (23.0)	-7.6 (23.2)
Pain: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		2.0 (18.0)	0.0 (16.3)	9.3 (21.8)	-1.3 (20.4)
Pain: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		-0.3 (19.7)	0.9 (21.2)	6.9 (15.7)	-4.6 (12.5)
Pain: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		0.7 (20.2)	2.5 (19.6)	1.1 (14.7)	-5.6 (8.3)
Pain: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		-2.5 (18.7)	4.6 (25.9)	4.4 (14.7)	-9.7 (21.9)
Pain: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		-1.2 (17.9)	11.3 (22.4)	3.3 (13.1)	-13.0 (21.7)
Pain: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	9 participants	5 participants
		-4.5 (18.0)	8.8 (22.9)	1.9 (13.0)	-10.0 (25.3)
Pain: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		2.9 (19.8)	6.9 (31.3)	6.7 (27.9)	-13.3 (32.1)
Pain: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		-2.4 (20.2)	8.3 (11.8)	5.6 (25.5)	0.0 (0.0)
Pain: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		-22.2 (19.2)	0.0 [1] (NA)		8.3 (11.8)
Pain: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		-8.3 (11.8)	0.0 [1] (NA)
Pain: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		-22.2 (19.2)
Pain: Change at PT/Discontin.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		12.5 (14.8)	-33.3 [1] (NA)	-2.8 (19.5)	0.0 [1] (NA)
Physical functioning: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		92.7 (11.0)	92.3 (11.6)	91.3 (13.6)	92.7 (13.1)
Physical functioning: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		-4.4 (8.7)	0.3 (4.4)	-5.0 (6.7)	-2.5 (11.6)
Physical functioning: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	80 participants	84 participants
		-9.7 (17.4)	-0.2 (8.2)	-7.4 (15.0)	-1.5 (6.5)
Physical functioning: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		-10.3 (16.6)	-0.6 (7.0)	-10.2 (15.3)	-2.7 (9.7)
Physical functioning: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	83 participants	84 participants
		-6.2 (14.4)	-0.3 (9.1)	-9.2 (16.9)	-1.8 (8.2)
Physical functioning: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	81 participants
		-7.1 (16.4)	-0.7 (10.8)	-7.6 (13.9)	-1.4 (9.4)
Physical functioning: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		-6.6 (14.8)	-0.7 (11.0)	-7.3 (15.0)	-2.7 (10.4)
Physical functioning: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		-4.9 (13.1)	-0.2 (10.8)	-7.4 (13.8)	-1.0 (10.3)
Physical functioning: Change at Cycle 5 Day 1	Number Analyzed	110 participants	117 participants	72 participants	64 participants
		-6.1 (14.7)	-1.0 (11.3)	-5.6 (13.3)	-1.8 (12.7)
Physical functioning: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		-4.7 (14.5)	-0.8 (12.1)	-7.5 (15.2)	-0.6 (10.0)
Physical functioning: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		-4.7 (13.6)	0.4 (11.2)	-8.0 (12.7)	0.2 (9.5)
Physical functioning: Change at Cycle 8 Day 1	Number Analyzed	105 participants	106 participants	65 participants	53 participants
		-5.2 (13.6)	-0.8 (13.1)	-6.7 (12.6)	-0.3 (11.0)
Physical functioning: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		-6.7 (18.2)	-0.5 (12.2)	-5.5 (10.6)	-1.5 (14.7)
Physical functioning: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		-4.9 (14.0)	-1.6 (11.8)	-6.5 (13.2)	-1.7 (9.9)
Physical functioning: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		-4.2 (14.4)	-1.3 (10.8)	-6.0 (12.8)	-3.3 (13.5)
Physical functioning: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		-5.4 (15.7)	-1.6 (11.5)	-4.8 (11.9)	-0.6 (10.8)
Physical functioning: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		-4.5 (15.0)	-3.0 (14.7)	-5.6 (12.4)	-1.9 (12.3)
Physical functioning: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		-2.8 (13.3)	-2.9 (16.0)	-5.8 (13.8)	-5.1 (14.7)
Physical functioning: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		0.5 (11.3)	0.1 (9.8)	-0.8 (10.9)	-0.5 (12.6)
Physical functioning: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		-1.9 (12.5)	0.0 (8.5)	-4.1 (10.5)	0.6 (12.6)
Physical functioning: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	42 participants	33 participants
		0.4 (10.7)	-1.7 (13.5)	-3.3 (13.4)	0.6 (8.1)
Physical functioning: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		-1.4 (10.0)	-0.5 (11.7)	-1.4 (9.6)	-1.1 (14.2)
Physical functioning: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		-0.9 (8.6)	-2.6 (13.6)	2.7 (9.7)	-0.4 (10.3)
Physical functioning: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		-0.5 (8.6)	-1.0 (10.8)	2.7 (10.0)	-3.7 (11.6)
Physical functioning: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		0.2 (7.2)	-3.4 (12.9)	-0.9 (10.3)	0.0 (17.5)
Physical functioning: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		2.5 (8.3)	-4.9 (10.3)	1.3 (11.2)	1.5 (18.2)
Physical functioning: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	9 participants	5 participants
		1.2 (8.1)	-7.1 (14.2)	0.7 (13.1)	2.7 (19.2)
Physical functioning: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		-1.2 (4.2)	-5.0 (11.4)	-2.7 (10.1)	5.3 (20.2)
Physical functioning: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		0.0 (8.6)	0.0 (0.0)	-4.4 (20.4)	-3.3 (4.7)
Physical functioning: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		2.2 (3.8)	0.0 [1] (NA)		-6.7 (9.4)
Physical functioning: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		3.3 (4.7)	0.0 [1] (NA)
Physical functioning: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		2.2 (3.8)
Physical functioning: Change at PT/Discontin.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		-0.8 (8.3)	0.0 [2] (NA)	10.0 (15.6)	0.0 [1] (NA)
Global health status/QoL: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		79.0 (16.7)	77.9 (18.4)	76.5 (20.6)	78.8 (17.6)
Global health status/QoL: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		-9.4 (20.5)	0.4 (7.5)	-9.9 (15.9)	1.3 (6.4)
Global health status/QoL: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	78 participants	83 participants
		-19.1 (24.2)	-0.4 (11.4)	-14.5 (20.4)	-0.3 (11.7)
Global health status/QoL: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		-17.8 (27.0)	1.2 (10.3)	-16.7 (19.9)	0.5 (11.2)
Global health status/QoL: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	82 participants	84 participants
		-9.8 (19.7)	-1.2 (14.5)	-10.9 (17.6)	1.0 (10.8)
Global health status/QoL: Change at Cycle 2 Day 15	Number Analyzed	118 participants	134 participants	80 participants	80 participants
		-11.5 (21.0)	0.2 (13.5)	-9.5 (18.0)	-1.4 (14.4)
Global health status/QoL: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		-10.6 (19.0)	-1.0 (14.6)	-9.4 (17.0)	-0.9 (14.6)
Global health status/QoL: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		-10.2 (19.6)	-1.0 (14.9)	-8.4 (18.9)	-1.8 (15.4)
Global health status/QoL: Change at Cycle 5 Day 1	Number Analyzed	110 participants	116 participants	72 participants	64 participants
		-12.0 (20.4)	-0.1 (15.1)	-8.9 (17.3)	0.4 (16.6)
Global health status/QoL: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		-8.9 (18.9)	-2.2 (16.1)	-12.4 (19.3)	-0.5 (16.5)
Global health status/QoL: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		-10.7 (19.4)	-1.6 (16.8)	-11.8 (17.9)	-2.3 (15.8)
Global health status/QoL: Change at Cycle 8 Day 1	Number Analyzed	104 participants	106 participants	65 participants	53 participants
		-10.3 (18.3)	-1.6 (17.6)	-11.2 (20.5)	-3.3 (17.0)
Global health status/QoL: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		-11.3 (21.9)	-0.5 (16.9)	-8.3 (19.7)	-1.6 (16.6)
Global health status/QoL: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		-7.6 (19.1)	-0.7 (15.9)	-9.8 (18.7)	0.2 (15.0)
Global health status/QoL: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		-7.8 (19.5)	-0.8 (15.3)	-8.8 (18.9)	-3.1 (18.2)
Global health status/QoL: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		-9.3 (20.2)	-0.8 (16.0)	-10.5 (17.4)	-3.6 (18.0)
Global health status/QoL: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		-7.5 (17.5)	-3.4 (19.4)	-9.4 (18.9)	-3.9 (15.8)
Global health status/QoL: Change at EOT	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		-5.2 (19.0)	-3.6 (19.0)	-3.0 (18.4)	-7.4 (21.7)
Global health status/QoL: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		0.1 (16.0)	-0.1 (15.7)	-1.0 (18.1)	0.2 (20.0)
Global health status/QoL: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		-2.2 (16.2)	0.5 (14.8)	0.4 (19.5)	0.0 (19.7)
Global health status/QoL: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	41 participants	33 participants
		-4.1 (21.6)	-0.9 (15.2)	-0.4 (16.9)	-1.3 (19.9)
Global health status/QoL: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		-2.3 (15.6)	-0.7 (15.3)	2.2 (13.2)	-2.0 (23.6)
Global health status/QoL: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		-0.9 (17.7)	-2.0 (15.1)	1.5 (15.1)	-0.5 (17.7)
Global health status/QoL: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		-0.9 (15.6)	-1.5 (15.8)	1.7 (14.8)	-0.9 (13.5)
Global health status/QoL: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		0.3 (17.4)	-2.6 (17.6)	6.1 (15.3)	-2.1 (24.7)
Global health status/QoL: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		1.2 (14.9)	-4.7 (19.4)	-3.3 (19.3)	0.0 (29.2)
Global health status/QoL: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	8 participants	5 participants
		0.4 (20.5)	2.5 (15.0)	-1.0 (13.7)	6.7 (21.6)
Global health status/QoL: Change at PT 130 Weeks	Number Analyzed	16 participants	12 participants	5 participants	5 participants
		2.1 (7.1)	-3.5 (16.8)	-3.3 (12.6)	5.0 (24.0)
Global health status/QoL: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		-1.2 (18.9)	-4.2 (5.9)	-11.1 (9.6)	-8.3 (11.8)
Global health status/QoL: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		11.1 (4.8)	0.0 [2] (NA)		12.5 (5.9)
Global health status/QoL: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		8.3 (0.0)	0.0 [1] (NA)
Global health status/QoL: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		19.4 (12.7)
Global health status/QoL: Change at PT/Discontin.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		-4.2 (19.9)	0.0 [1] (NA)	0.0 (31.2)	0.0 [1] (NA)
Role functioning: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		86.7 (21.9)	87.2 (22.5)	86.6 (22.0)	88.6 (23.2)
Role functioning: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		-2.8 (15.3)	-0.8 (10.9)	-1.0 (16.6)	4.4 (18.3)
Role functioning: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	80 participants	84 participants
		-19.4 (29.1)	0.2 (16.3)	-15.2 (27.6)	-2.4 (19.6)
Role functioning: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		-10.6 (28.4)	1.6 (9.0)	-16.7 (20.9)	-1.0 (25.3)
Role functioning: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	83 participants	84 participants
		-13.0 (26.6)	0.2 (16.6)	-13.3 (27.5)	0.4 (17.5)
Role functioning: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	81 participants
		-11.1 (25.7)	-0.6 (18.4)	-9.6 (21.5)	-0.4 (17.5)
Role functioning: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		-9.7 (25.4)	0.4 (19.0)	-8.2 (21.3)	-2.1 (21.2)
Role functioning: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		-8.4 (23.8)	0.3 (21.3)	-9.0 (19.7)	-1.3 (19.0)
Role functioning: Change at Cycle 5 Day 1	Number Analyzed	110 participants	117 participants	72 participants	64 participants
		-11.1 (26.0)	0.6 (20.5)	-10.4 (22.3)	0.8 (22.7)
Role functioning: Change at Cycle 6 Day 1	Number Analyzed	106 participants	111 participants	69 participants	63 participants
		-5.8 (24.2)	-0.5 (18.3)	-11.6 (22.9)	0.5 (20.1)
Role functioning: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		-9.9 (27.6)	0.9 (21.5)	-8.8 (24.0)	0.3 (21.3)
Role functioning: Change at Cycle 8 Day 1	Number Analyzed	105 participants	105 participants	65 participants	53 participants
		-9.2 (26.5)	-1.9 (23.0)	-9.5 (24.5)	-0.3 (21.3)
Role functioning: Change at Cycle 9 Day 1	Number Analyzed	100 participants	100 participants	63 participants	52 participants
		-11.2 (28.4)	0.0 (20.7)	-7.9 (23.5)	-1.9 (25.7)
Role functioning: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		-8.5 (25.5)	-1.7 (19.3)	-7.7 (23.2)	3.9 (22.3)
Role functioning: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		-6.6 (24.5)	-1.3 (19.7)	-10.2 (25.0)	-3.5 (24.8)
Role functioning: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		-8.7 (26.2)	-0.4 (17.2)	-8.2 (25.2)	0.3 (26.3)
Role functioning: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		-8.1 (24.6)	-4.5 (22.2)	-8.3 (25.9)	-2.2 (24.3)
Role functioning: Change at End Of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		-4.7 (25.0)	-1.3 (23.2)	-4.2 (25.0)	-6.0 (27.6)
Role functioning: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		2.0 (21.8)	1.8 (17.6)	1.2 (19.0)	5.3 (26.9)
Role functioning: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		0.9 (24.7)	3.0 (17.3)	0.4 (20.1)	5.2 (24.5)
Role functioning: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	42 participants	33 participants
		2.7 (24.2)	0.2 (21.1)	0.4 (21.3)	7.1 (28.0)
Role functioning: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		2.4 (23.8)	0.8 (20.3)	0.6 (18.2)	4.0 (29.0)
Role functioning: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		5.3 (19.3)	-1.3 (16.6)	3.9 (11.1)	7.4 (29.3)
Role functioning: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		-1.4 (25.5)	-4.0 (20.0)	4.4 (11.7)	-3.7 (13.9)
Role functioning: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		3.5 (27.2)	-1.7 (17.4)	1.1 (14.7)	16.7 (35.5)
Role functioning: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		6.2 (22.2)	-7.3 (20.5)	6.7 (14.1)	14.8 (38.6)
Role functioning: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	9 participants	5 participants
		7.6 (26.6)	-2.0 (10.0)	5.6 (11.8)	26.7 (41.8)
Role functioning: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		6.9 (21.3)	-5.6 (14.8)	3.3 (18.3)	23.3 (43.5)
Role functioning: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		7.1 (18.9)	0.0 (0.0)	11.1 (19.2)	8.3 (11.8)
Role functioning: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		27.8 (25.5)	0.0 [1] (NA)		16.7 (23.6)
Role functioning: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		16.7 (23.6)	0.0 [1] (NA)
Role functioning: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		27.8 (25.5)
Role functioning: Change at PT/Discontin.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		-8.3 (23.6)	0.0 [1] (NA)	11.1 (17.2)	0.0 [1] (NA)
Social functioning: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		89.6 (16.6)	88.2 (20.8)	87.7 (21.2)	90.4 (19.9)
Social functioning: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		1.4 (18.3)	0.8 (12.0)	2.1 (14.8)	0.9 (8.7)
Social functioning: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	78 participants	84 participants
		-15.0 (26.9)	0.8 (13.8)	-7.5 (18.9)	0.4 (13.4)
Social functioning: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		-9.1 (28.0)	5.6 (13.3)	-5.6 (17.4)	-2.0 (20.3)
Social functioning: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	82 participants	84 participants
		-8.0 (22.9)	2.2 (16.6)	-10.2 (23.8)	3.0 (13.7)
Social functioning: Change at Cycle 2 Day 15	Number Analyzed	118 participants	134 participants	80 participants	80 participants
		-8.3 (21.5)	2.7 (16.9)	-7.7 (18.2)	4.0 (17.0)
Social functioning: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		-8.1 (21.5)	2.3 (17.8)	-7.4 (21.1)	1.5 (17.9)
Social functioning: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	76 participants
		-7.1 (21.5)	1.7 (18.1)	-7.5 (20.6)	1.3 (13.5)
Social functioning: Change at Cycle 5 Day 1	Number Analyzed	110 participants	116 participants	72 participants	64 participants
		-9.4 (21.7)	3.3 (17.6)	-9.5 (18.5)	2.6 (18.6)
Social functioning: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	69 participants	63 participants
		-7.2 (22.2)	1.9 (17.6)	-11.4 (22.4)	0.0 (17.2)
Social functioning: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		-8.0 (22.7)	4.5 (17.0)	-9.6 (22.9)	0.0 (17.2)
Social functioning: Change at Cycle 8 Day 1	Number Analyzed	104 participants	106 participants	65 participants	53 participants
		-8.3 (23.6)	2.2 (17.7)	-7.9 (23.0)	0.6 (16.0)
Social functioning: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		-11.0 (26.2)	1.7 (19.7)	-8.2 (22.8)	-3.8 (21.5)
Social functioning: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		-8.7 (24.9)	0.0 (16.1)	-8.7 (23.4)	-0.7 (16.3)
Social functioning: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		-8.6 (24.4)	1.4 (15.1)	-9.9 (23.1)	-2.1 (21.6)
Social functioning: Change at Cycle 12 Day 1	Number Analyzed	90 participants	91 participants	55 participants	48 participants
		-10.6 (24.2)	-0.4 (15.7)	-9.1 (22.2)	0.0 (16.5)
Social functioning: Change at Cycle 13 Day 1	Number Analyzed	82 participants	89 participants	54 participants	45 participants
		-8.3 (24.2)	-1.9 (21.1)	-10.2 (25.2)	1.5 (17.7)
Social functioning: Change at End of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		-6.1 (21.8)	1.2 (25.8)	-5.5 (23.3)	-3.3 (21.2)
Social functioning: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		-1.7 (18.9)	2.7 (15.4)	1.2 (16.2)	1.3 (19.5)
Social functioning: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		-2.6 (20.3)	4.2 (15.0)	0.0 (13.9)	2.4 (14.1)
Social functioning: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	41 participants	33 participants
		3.4 (16.5)	2.7 (15.4)	0.0 (18.3)	5.1 (17.4)
Social functioning: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		-0.7 (18.9)	1.6 (14.7)	2.5 (13.6)	-1.3 (18.0)
Social functioning: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		2.8 (18.7)	0.9 (16.0)	4.9 (11.4)	0.9 (10.7)
Social functioning: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		0.7 (20.8)	6.1 (14.3)	4.4 (13.3)	-1.9 (13.0)
Social functioning: Change at PT 91 Weeks	Number Analyzed	32 participants	29 participants	15 participants	12 participants
		2.6 (21.6)	1.7 (20.1)	2.2 (13.9)	2.8 (12.0)
Social functioning: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		2.5 (18.3)	0.0 (19.2)	3.3 (10.5)	1.9 (13.0)
Social functioning: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	8 participants	5 participants
		9.1 (15.2)	2.0 (21.1)	-2.1 (5.9)	3.3 (18.3)
Social functioning: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		9.8 (15.7)	6.9 (16.6)	0.0 (0.0)	10.0 (32.5)
Social functioning: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		7.1 (18.9)	0.0 (0.0)	0.0 (0.0)	-8.3 (11.8)
Social functioning: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		27.8 (9.6)	0.0 [1] (NA)		0.0 (0.0)
Social functioning: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		25.0 (11.8)	0.0 [1] (NA)
Social functioning: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		27.8 (9.6)
Social functioning: Change at PT/Discontinuation	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		-4.2 (21.4)	0.0 [1] (NA)	0.0 (10.5)	0.0 [1] (NA)
Insomnia: Cycle 1 Day 1 (Baseline)	Number Analyzed	138 participants	147 participants	87 participants	89 participants
		18.4 (23.2)	17.0 (25.4)	17.2 (23.2)	18.7 (24.6)
Insomnia: Change at Cycle 1 Day 8	Number Analyzed	24 participants	22 participants	16 participants	19 participants
		11.1 (18.8)	-3.0 (14.2)	2.1 (22.7)	1.8 (20.7)
Insomnia: Change at Cycle 1 Day 15	Number Analyzed	132 participants	139 participants	80 participants	84 participants
		6.8 (29.6)	1.0 (19.6)	9.6 (26.1)	-4.4 (21.2)
Insomnia: Change at Cycle 1 Day 22	Number Analyzed	22 participants	21 participants	15 participants	17 participants
		9.1 (27.6)	-3.2 (23.3)	6.7 (18.7)	-7.8 (22.1)
Insomnia: Change at Cycle 2 Day 1	Number Analyzed	127 participants	142 participants	83 participants	84 participants
		0.8 (23.9)	-1.2 (22.6)	2.4 (24.8)	-5.6 (19.9)
Insomnia: Change at Cycle 2 Day 15	Number Analyzed	119 participants	134 participants	80 participants	81 participants
		5.9 (27.7)	0.5 (25.2)	2.1 (28.7)	-3.7 (23.0)
Insomnia: Change at Cycle 3 Day 1	Number Analyzed	119 participants	129 participants	81 participants	78 participants
		0.6 (25.7)	-1.3 (23.0)	-0.4 (28.1)	-2.6 (22.0)
Insomnia: Change at Cycle 4 Day 1	Number Analyzed	119 participants	129 participants	78 participants	75 participants
		2.2 (25.6)	-1.0 (25.0)	3.4 (26.1)	-4.9 (23.1)
Insomnia: Change at Cycle 5 Day 1	Number Analyzed	110 participants	117 participants	72 participants	64 participants
		2.4 (27.4)	0.3 (23.8)	3.2 (26.9)	-5.7 (22.7)
Insomnia: Change at Cycle 6 Day 1	Number Analyzed	106 participants	112 participants	68 participants	63 participants
		3.1 (28.6)	1.8 (25.6)	3.4 (26.5)	-4.2 (24.3)
Insomnia: Change at Cycle 7 Day 1	Number Analyzed	106 participants	108 participants	68 participants	59 participants
		4.7 (26.6)	-0.3 (25.6)	3.4 (23.8)	-2.3 (17.4)
Insomnia: Change at Cycle 8 Day 1	Number Analyzed	104 participants	106 participants	65 participants	53 participants
		4.2 (28.5)	0.6 (29.1)	7.7 (29.9)	-6.3 (18.6)
Insomnia: Change at Cycle 9 Day 1	Number Analyzed	100 participants	101 participants	63 participants	52 participants
		3.3 (27.8)	0.7 (27.1)	6.3 (28.6)	0.0 (21.9)
Insomnia: Change at Cycle 10 Day 1	Number Analyzed	96 participants	97 participants	63 participants	47 participants
		1.7 (22.9)	0.7 (22.0)	4.2 (27.1)	-1.4 (19.6)
Insomnia: Change at Cycle 11 Day 1	Number Analyzed	93 participants	93 participants	57 participants	48 participants
		0.7 (25.0)	-0.7 (25.5)	5.3 (32.0)	1.4 (18.1)
Insomnia: Change at Cycle 12 Day 1	Number Analyzed	89 participants	91 participants	55 participants	48 participants
		0.7 (24.6)	0.0 (27.7)	3.6 (29.2)	0.0 (23.8)
Insomnia: Change at Cycle 13 Day 1	Number Analyzed	82 participants	88 participants	54 participants	45 participants
		4.1 (26.4)	3.8 (31.7)	6.2 (29.0)	-1.5 (22.4)
Insomnia: Change at End Of Treatment	Number Analyzed	123 participants	125 participants	67 participants	75 participants
		-3.0 (25.3)	1.3 (28.8)	3.5 (32.4)	0.4 (26.6)
Insomnia: Change at PT 13 Weeks	Number Analyzed	90 participants	74 participants	56 participants	38 participants
		-4.4 (21.9)	-1.8 (25.2)	-2.4 (24.5)	-0.9 (22.6)
Insomnia: Change at PT 26 Weeks	Number Analyzed	90 participants	72 participants	47 participants	35 participants
		-2.6 (21.9)	0.5 (28.2)	-1.4 (23.0)	-3.8 (22.5)
Insomnia: Change at PT 39 Weeks	Number Analyzed	79 participants	68 participants	42 participants	33 participants
		-5.9 (23.7)	-0.5 (29.6)	-2.4 (27.9)	-5.1 (23.7)
Insomnia: Change at PT 52 Weeks	Number Analyzed	76 participants	62 participants	27 participants	25 participants
		-3.9 (24.3)	0.5 (26.6)	-2.5 (26.0)	-8.0 (26.0)
Insomnia: Change at PT 65 Weeks	Number Analyzed	53 participants	38 participants	17 participants	18 participants
		-6.3 (23.6)	1.8 (21.8)	-3.9 (33.1)	-3.7 (22.5)
Insomnia: Change at PT 78 Weeks	Number Analyzed	46 participants	33 participants	15 participants	9 participants
		-2.2 (28.5)	1.0 (30.6)	-4.4 (27.8)	-3.7 (26.1)
Insomnia: Change at PT 91 Weeks	Number Analyzed	33 participants	29 participants	15 participants	12 participants
		-4.0 (16.2)	-1.1 (25.9)	-4.4 (21.3)	-2.8 (26.4)
Insomnia: Change at PT 104 Weeks	Number Analyzed	27 participants	25 participants	10 participants	9 participants
		-4.9 (17.8)	4.0 (27.8)	0.0 (22.2)	-3.7 (11.1)
Insomnia: Change at PT 117 Weeks	Number Analyzed	22 participants	17 participants	9 participants	5 participants
		-9.1 (18.3)	-7.8 (30.1)	0.0 (16.7)	-13.3 (29.8)
Insomnia: Change at PT 130 Weeks	Number Analyzed	17 participants	12 participants	5 participants	5 participants
		-7.8 (22.1)	-8.3 (20.7)	6.7 (27.9)	-6.7 (14.9)
Insomnia: Change at PT 143 Weeks	Number Analyzed	7 participants	2 participants	3 participants	2 participants
		-14.3 (17.8)	-16.7 (23.6)	0.0 (33.3)	0.0 (0.0)
Insomnia: Change at PT 156 Weeks	Number Analyzed	3 participants	1 participants	0 participants	2 participants
		-11.1 (19.2)	0.0 [1] (NA)		0.0 (0.0)
Insomnia: Change at PT 169 Weeks	Number Analyzed	2 participants	1 participants	0 participants	0 participants
		0.0 (0.0)	0.0 [1] (NA)
Insomnia: Change at PT 182 Weeks	Number Analyzed	3 participants	0 participants	0 participants	0 participants
		-11.1 (19.2)
Insomnia: Change at PT/Discont.	Number Analyzed	8 participants	1 participants	6 participants	1 participants
		0.0 (17.8)	0.0 [1] (NA)	5.6 (25.1)	0.0 [1] (NA)

[1]

1 participant was analyzed, so standard deviation is not applicable.

[2]

1 participant was analyzed, so standard deviation is not applicable

6. Secondary Outcome

Title	Plasma Concentration of Vemurafenib
Description	[Not Specified]
Time Frame	Pre-morning dose (0 hour [hr]) and 1 to 4 hrs post-dose on Days 1, 8, 15, and 22 of Cycle 1; pre-morning dose (0 hr) on Days 1 and 15 of Cycle 2; pre-morning dose (0 hr) on Day 1 of Cycles 3-13; at end of treatment (up to 13 months)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK)-evaluable population included all participants who received at least one dose of vemurafenib and had provided valid PK assessments.

Arm/Group Title		Cohort 1 Vemurafenib	Cohort 2 Vemurafenib
Arm/Group Description:		Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks
Overall Number of Participants Analyzed		149	92
Mean (Standard Deviation); Unit of Measure: nanograms per milliliter (ng/mL)
Cycle 1 Day 1 (nominal Day 1)	Number Analyzed	122 participants	77 participants
		2880 (2770)	3050 (3010)
Cycle 1 Day 8	Number Analyzed	79 participants	52 participants
		49900 (19800)	43400 (13600)
Cycle 1 Day 15	Number Analyzed	55 participants	43 participants
		45300 (23000)	50200 (20500)
Cycle 1 Day 22	Number Analyzed	49 participants	45 participants
		44000 (22400)	48800 (23700)
Cycle 2 Day 1	Number Analyzed	107 participants	69 participants
		40200 (24100)	43800 (19400)
Cycle 2 Day 15	Number Analyzed	102 participants	68 participants
		42400 (21700)	44200 (21200)
Cycle 3 Day 1	Number Analyzed	100 participants	69 participants
		46700 (21500)	43700 (22000)
Cycle 4 Day 1	Number Analyzed	98 participants	68 participants
		44800 (19300)	47400 (20100)
Cycle 5 Day 1	Number Analyzed	92 participants	61 participants
		43100 (18800)	43700 (19400)
Cycle 6 Day 1	Number Analyzed	82 participants	62 participants
		46000 (18900)	42000 (22000)
Cycle 7 Day 1	Number Analyzed	86 participants	57 participants
		42800 (20500)	45200 (20500)
Cycle 8 Day 1	Number Analyzed	81 participants	55 participants
		43600 (19900)	42600 (18900)
Cycle 9 Day 1	Number Analyzed	77 participants	51 participants
		42900 (18400)	43000 (17700)
Cycle 10 Day 1	Number Analyzed	38 participants	29 participants
		41000 (19000)	43900 (18500)
Cycle 11 Day 1	Number Analyzed	35 participants	35 participants
		45900 (15300)	39700 (17600)
Cycle 12 Day 1	Number Analyzed	34 participants	26 participants
		43700 (15200)	46600 (19800)
Cycle 13 Day 1	Number Analyzed	36 participants	26 participants
		44000 (17200)	42600 (19900)

Adverse Events

Time Frame	Up to the data cutoff of July 13, 2018 (approximately 6 years).
Adverse Event Reporting Description	The safety population included all participants who received at least one dose of study medication.
Arm/Group Title	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
Arm/Group Description	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks	Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks
All-Cause Mortality
	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	18/154 (11.69%)	33/156 (21.15%)	25/93 (26.88%)	26/91 (28.57%)
Serious Adverse Events
	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	25/154 (16.23%)	16/156 (10.26%)	15/93 (16.13%)	9/91 (9.89%)
Blood and lymphatic system disorders
Lymphadenopathy * 1	0/154 (0.00%)	0/156 (0.00%)	0/93 (0.00%)	1/91 (1.10%)
Cardiac disorders
Pericarditis * 1	1/154 (0.65%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Atrial fibrillation * 1	0/154 (0.00%)	0/156 (0.00%)	2/93 (2.15%)	0/91 (0.00%)
Coronary artery occlusion * 1	0/154 (0.00%)	0/156 (0.00%)	0/93 (0.00%)	1/91 (1.10%)
Myocardial infarction * 1	0/154 (0.00%)	0/156 (0.00%)	0/93 (0.00%)	1/91 (1.10%)
Ear and labyrinth disorders
Vertigo positional * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Eye disorders
Iridocyclitis * 1	0/154 (0.00%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Gastrointestinal disorders
Leukoplakia oral * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Pancreatitis * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Pancreatitis acute * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Inguinal hernia * 1	0/154 (0.00%)	0/156 (0.00%)	0/93 (0.00%)	1/91 (1.10%)
General disorders
Chest pain * 1	0/154 (0.00%)	1/156 (0.64%)	1/93 (1.08%)	0/91 (0.00%)
Hepatobiliary disorders
Bile duct stone * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	0/91 (0.00%)
Hepatic function abnormal * 1	0/154 (0.00%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Infections and infestations
Appendicitis * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	0/91 (0.00%)
Bronchitis * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Cellulitis * 1	0/154 (0.00%)	2/156 (1.28%)	0/93 (0.00%)	1/91 (1.10%)
Groin infection * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Hepatitis B * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	0/91 (0.00%)
Infection * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Soft tissue infection * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Erysipelas * 1	0/154 (0.00%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Infected skin ulcer * 1	0/154 (0.00%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Investigations
Electrocardiogram QT prolonged * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Lipase increased * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Metabolism and nutrition disorders
Hyperlipasaemia * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Hypokalaemia * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Hypophosphataemia * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	0/91 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	2/154 (1.30%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Dupuytren's contracture * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute promyelocytic leukaemia * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	0/91 (0.00%)
Atypical fibroxanthoma * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	0/91 (0.00%)
Basal cell carcinoma * 1	6/154 (3.90%)	7/156 (4.49%)	3/93 (3.23%)	1/91 (1.10%)
Malignant melanoma * 1	1/154 (0.65%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Prostate cancer * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	2/91 (2.20%)
Squamous cell carcinoma of skin * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Thyroid cancer * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Gastrointestinal stromal tumour * 1	0/154 (0.00%)	0/156 (0.00%)	0/93 (0.00%)	1/91 (1.10%)
Neuroendocrine carcinoma * 1	0/154 (0.00%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Pancreatic neuroendocrine tumour * 1	0/154 (0.00%)	0/156 (0.00%)	0/93 (0.00%)	1/91 (1.10%)
Nervous system disorders
Carotid artery stenosis * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Facial paralysis * 1	1/154 (0.65%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Psychiatric disorders
Suicidal ideation * 1	0/154 (0.00%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pleuritic pain * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Pneumothorax * 1	0/154 (0.00%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Skin and subcutaneous tissue disorders
Actinic keratosis * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Dermatitis exfoliative * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Drug reaction with eosinophilia and systemic symptoms * 1	1/154 (0.65%)	0/156 (0.00%)	1/93 (1.08%)	0/91 (0.00%)
Rash * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Rash papular * 1	1/154 (0.65%)	0/156 (0.00%)	0/93 (0.00%)	0/91 (0.00%)
Vascular disorders
Hypotension * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	0/91 (0.00%)
Pelvic venous thrombosis * 1	0/154 (0.00%)	1/156 (0.64%)	0/93 (0.00%)	0/91 (0.00%)
Hypertension * 1	0/154 (0.00%)	1/156 (0.64%)	1/93 (1.08%)	0/91 (0.00%)
1 Term from vocabulary, MedDRA, Version 19.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort 1 Vemurafenib	Cohort 1 Placebo	Cohort 2 Vemurafenib	Cohort 2 Placebo
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	150/154 (97.40%)	117/156 (75.00%)	92/93 (98.92%)	67/91 (73.63%)
Gastrointestinal disorders
Nausea * 1	59/154 (38.31%)	36/156 (23.08%)	27/93 (29.03%)	9/91 (9.89%)
Diarrhoea * 1	38/154 (24.68%)	32/156 (20.51%)	27/93 (29.03%)	9/91 (9.89%)
Vomiting * 1	19/154 (12.34%)	9/156 (5.77%)	14/93 (15.05%)	4/91 (4.40%)
Constipation * 1	8/154 (5.19%)	11/156 (7.05%)	9/93 (9.68%)	3/91 (3.30%)
Abdominal pain * 1	10/154 (6.49%)	7/156 (4.49%)	6/93 (6.45%)	2/91 (2.20%)
General disorders
Fatigue * 1	52/154 (33.77%)	52/156 (33.33%)	26/93 (27.96%)	18/91 (19.78%)
Asthenia * 1	24/154 (15.58%)	13/156 (8.33%)	17/93 (18.28%)	10/91 (10.99%)
Pyrexia * 1	28/154 (18.18%)	11/156 (7.05%)	16/93 (17.20%)	7/91 (7.69%)
Oedema peripheral * 1	9/154 (5.84%)	8/156 (5.13%)	7/93 (7.53%)	4/91 (4.40%)
Infections and infestations
Nasopharyngitis * 1	9/154 (5.84%)	10/156 (6.41%)	4/93 (4.30%)	7/91 (7.69%)
Injury, poisoning and procedural complications
Sunburn * 1	25/154 (16.23%)	2/156 (1.28%)	19/93 (20.43%)	2/91 (2.20%)
Investigations
Alanine aminotransferase increased * 1	28/154 (18.18%)	5/156 (3.21%)	14/93 (15.05%)	4/91 (4.40%)
Aspartate aminotransferase increased * 1	18/154 (11.69%)	5/156 (3.21%)	11/93 (11.83%)	3/91 (3.30%)
Metabolism and nutrition disorders
Decreased appetite * 1	17/154 (11.04%)	11/156 (7.05%)	16/93 (17.20%)	2/91 (2.20%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	101/154 (65.58%)	37/156 (23.72%)	49/93 (52.69%)	17/91 (18.68%)
Pain in extremity * 1	31/154 (20.13%)	15/156 (9.62%)	17/93 (18.28%)	4/91 (4.40%)
Myalgia * 1	23/154 (14.94%)	10/156 (6.41%)	9/93 (9.68%)	3/91 (3.30%)
Musculoskeletal pain * 1	9/154 (5.84%)	8/156 (5.13%)	7/93 (7.53%)	4/91 (4.40%)
Back pain * 1	5/154 (3.25%)	14/156 (8.97%)	7/93 (7.53%)	2/91 (2.20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma * 1	21/154 (13.64%)	2/156 (1.28%)	19/93 (20.43%)	2/91 (2.20%)
Seborrhoeic keratosis * 1	13/154 (8.44%)	7/156 (4.49%)	10/93 (10.75%)	1/91 (1.10%)
Keratoacanthoma * 1	14/154 (9.09%)	0/156 (0.00%)	10/93 (10.75%)	2/91 (2.20%)
Nervous system disorders
Headache * 1	29/154 (18.83%)	32/156 (20.51%)	20/93 (21.51%)	11/91 (12.09%)
Dysgeusia * 1	17/154 (11.04%)	4/156 (2.56%)	8/93 (8.60%)	3/91 (3.30%)
Psychiatric disorders
Insomnia * 1	9/154 (5.84%)	7/156 (4.49%)	12/93 (12.90%)	4/91 (4.40%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	14/154 (9.09%)	8/156 (5.13%)	6/93 (6.45%)	3/91 (3.30%)
Skin and subcutaneous tissue disorders
Rash * 1	57/154 (37.01%)	20/156 (12.82%)	34/93 (36.56%)	10/91 (10.99%)
Alopecia * 1	57/154 (37.01%)	10/156 (6.41%)	37/93 (39.78%)	4/91 (4.40%)
Pruritus * 1	44/154 (28.57%)	27/156 (17.31%)	28/93 (30.11%)	3/91 (3.30%)
Hyperkeratosis * 1	52/154 (33.77%)	6/156 (3.85%)	35/93 (37.63%)	0/91 (0.00%)
Photosensitivity reaction * 1	58/154 (37.66%)	5/156 (3.21%)	25/93 (26.88%)	4/91 (4.40%)
Dry skin * 1	32/154 (20.78%)	13/156 (8.33%)	16/93 (17.20%)	5/91 (5.49%)
Erythema * 1	20/154 (12.99%)	8/156 (5.13%)	17/93 (18.28%)	6/91 (6.59%)
Actinic keratosis * 1	15/154 (9.74%)	8/156 (5.13%)	4/93 (4.30%)	2/91 (2.20%)
1 Term from vocabulary, MedDRA, Version 19.1; * 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.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 1-800-821-8590
• EMail: genentech@druginfo.com

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

Ascierto PA, Lewis KD, Di Giacomo AM, Demidov L, Mandala M, Bondarenko I, Herbert C, Mackiewicz A, Rutkowski P, Guminski A, Simmons B, Ye C, Hooper G, Wongchenko MJ, Goodman GR, Yan Y, Schadendorf D. Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAFv600 mutation-positive melanoma receiving adjuvant vemurafenib. Ann Oncol. 2020 Jan;31(1):153-159. doi: 10.1016/j.annonc.2019.10.002.

Maio M, Lewis K, Demidov L, Mandala M, Bondarenko I, Ascierto PA, Herbert C, Mackiewicz A, Rutkowski P, Guminski A, Goodman GR, Simmons B, Ye C, Yan Y, Schadendorf D; BRIM8 Investigators. Adjuvant vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):510-520. doi: 10.1016/S1470-2045(18)30106-2. Epub 2018 Feb 21. Erratum In: Lancet Oncol. 2018 Apr;19(4):e184.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01667419
• Other Study ID Numbers: GO27826; 2011-004011-24 ( EudraCT Number )
• First Submitted: August 15, 2012
• First Posted: August 17, 2012
• Results First Submitted: June 5, 2018
• Results First Posted: October 17, 2018
• Last Update Posted: July 23, 2019