Ph II Study to Evaluate Olaparib With Abiraterone in Treating Metastatic Castration Resistant Prostate Cancer.

• ClinicalTrials.gov Identifier: NCT01972217
• Recruitment Status: Completed
• First Posted: October 30, 2013
• Results First Posted: October 2, 2018
• Last Update Posted: November 14, 2023
• Sponsor: AstraZeneca
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Metastatic Castration-resistant Prostate Cancer
• Interventions: Drug: Olaparib; Drug: Placebo; Drug: Abiraterone; Drug: Prednisone or prednisolone
• Enrollment: 158

Participant Flow

Recruitment Details	In this 2-part study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were recruited at 41 sites in Europe, Russia and North America. Part A had 2 cohorts for olaparib dose selection when given with approved treatment abiraterone. Part B compared olaparib versus placebo both with abiraterone in post-chemotherapy mCRPC patients.
Pre-assignment Details	Patients dosed in open-label Part A could not participate in Part B which was a randomised, double-blind, placebo-controlled comparison of olaparib + abiraterone versus placebo + abiraterone in patients who had received prior chemotherapy containing docetaxel.

Arm/Group Title	Part A Cohort 1: Olaparib 200 mg + Abiraterone	Part A Cohort 2: Olaparib 300 mg + Abiraterone	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description	Patients received olaparib 200 milligrams (mg) twice daily (bid) and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Period Title: Part A: Open-label Safety Run-in Period
Started	3	13	0	0
Completed	2	1	0	0
Not Completed	1	12	0	0
Reason Not Completed
Withdrawal by Subject	0	1	0	0
Condition under investigation worsened	1	9	0	0
Adverse Event	0	1	0	0
Death	0	1	0	0
Period Title: Part B Double-blind, Randomised Period
Started	0 [1]	0 [1]	71 [2]	71 [2]
Received Olaparib/Placebo	0	0	71	71
Received Abiraterone	0	0	71	71
Completed	0	0	25	24
Not Completed	0	0	46	47
Reason Not Completed
Death	0	0	43	44
Reason not recorded	0	0	1	0
Screen failure	0	0	0	1
Lost to Follow-up	0	0	2	1
Withdrawal by Subject	0	0	0	1
[1] Patients recruited to Part A did not participate in Part B.; [2] Patients recruited to Part B did not participate in Part A.

Baseline Characteristics

Arm/Group Title		Part A Cohort 1: Olaparib 200 mg + Abiraterone	Part A Cohort 2: Olaparib 300 mg + Abiraterone	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone	Total
Arm/Group Description		Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Total of all reporting groups
Overall Number of Baseline Participants		3	13	71	71	158
Baseline Analysis Population Description		The Safety analysis set consisted of all patients who received at least 1 dose of study treatment in Part A and all patients randomised into Part B of the study who received at least 1 dose of study treatment.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	13 participants	71 participants	71 participants	158 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	0 0.0%	3 23.1%	17 23.9%	22 31.0%	42 26.6%
	>=65 years	3 100.0%	10 76.9%	54 76.1%	49 69.0%	116 73.4%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	13 participants	71 participants	71 participants	158 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	3 100.0%	13 100.0%	71 100.0%	71 100.0%	158 100.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	13 participants	71 participants	71 participants	158 participants
	Hispanic or Latino	1 33.3%	0 0.0%	11 15.5%	5 7.0%	17 10.8%
	Not Hispanic or Latino	2 66.7%	13 100.0%	58 81.7%	63 88.7%	136 86.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	2 2.8%	3 4.2%	5 3.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	13 participants	71 participants	71 participants	158 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	1 1.4%	0 0.0%	1 0.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	1 1.4%	1 1.4%	2 1.3%
	White	3 100.0%	13 100.0%	67 94.4%	67 94.4%	150 94.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	2 2.8%	3 4.2%	5 3.2%

Outcome Measures

1. Primary Outcome

Title	Part A: Percentage of Patients Experiencing Adverse Events (AEs)
Description	The safety and tolerability of olaparib in combination with abiraterone was assessed during Part A of the study. The percentage of patients experiencing AEs, including information on seriousness, severity, study treatment relationship and those leading to discontinuation for all doses of olaparib and for abiraterone are presented. Severity of AEs was assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAE) v4.0. AEs were assigned to a Grade from 1 through 5 as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening requiring hospitalisation; Grade 4: Life-threatening consequences; Grade 5: Death related to AE. 'c-r' = causally related 'discont' = discontinuation.
Time Frame	Cohort 1 and 2: From baseline in Part A (Day 1 for each cohort) up to 30 days following last dose of study treatment.

Outcome Measure Data

Analysis Population Description

The Part A Safety analysis set consisted of all patients who received at least 1 dose of study treatment in Part A. Treatment group comparisons were based on the initial dose of olaparib actually received.

Arm/Group Title	Part A Cohort 1: Olaparib 200 mg + Abiraterone	Part A Cohort 2: Olaparib 300 mg + Abiraterone
Arm/Group Description:	Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	3	13
Measure Type: Number; Unit of Measure: Percentage of patients
Any AE c-r to olaparib + abiraterone	66.7	46.2
Any AE c-r to olaparib only	33.3	7.7
Any AE c-r to abiraterone only	0	15.4
Any AE CTCAE Grade 3 or higher	66.7	23.1
Any AE CTCAE Grade 3 or higher c-r to olaparib	0	7.7
Any AE CTCAE Grade 3 or higher c-r to abiraterone	0	7.7
Any AE with outcome = death	0	0
Any serious AE (SAE)	66.7	23.1
Any SAE c-r to olaparib	0	0
Any SAE c-r to abiraterone	0	0
Any AE causing discont of olaparib	0	7.7
Any AE causing discont of olaparib c-r to olaparib	0	0
Any AE causing discont olaparib c-r to abiraterone	0	0

2. Primary Outcome

Title	Part A: Number of Patients With Dose Limiting Toxicities (DLTs)
Description	DLTs were assessed by a Safety Review Committee (SRC) after a minimum of 3 patients had received at least 14 days of treatment in Part A. A DLT was defined as any toxicity which was not a recognised AE of abiraterone or prednisolone, and was not attributable to the disease or disease-related processes under investigation, which occurred during a minimum period of 14 days treatment and which included: 1. haematological toxicity CTCAE v4.0 Grade 4 or higher present for more than 4 days (except anaemia); 2. non-haematological toxicity CTCAE v4.0 Grade 3 or higher including infection, corrected QT interval prolongation; 3. any other toxicity that was greater than that at baseline, was clinically significant and/or unacceptable, did not respond to supportive care, resulted in a disruption of dosing schedule of 7 days or more, or was judged to be a DLT by the SRC. A DLT excluded alopecia and isolated laboratory changes of any grade without clinical sequelae or clinical significance.
Time Frame	From Day 1 for Cohort 1 and from Day 4 for Cohort 2 up to 14 days treatment with olaparib + abiraterone for 3 patients.

Outcome Measure Data

Analysis Population Description

The Part A Safety analysis set consisted of all patients who received at least 1 dose of study treatment in Part A. Treatment group comparisons were based on the initial dose of olaparib actually received.

Arm/Group Title	Part A Cohort 1: Olaparib 200 mg + Abiraterone	Part A Cohort 2: Olaparib 300 mg + Abiraterone
Arm/Group Description:	Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	3	13
Measure Type: Number; Unit of Measure: Patients
	2	4

3. Primary Outcome

Title	Part B: Median Radiological Progression-Free Survival (rPFS) Time
Description	The efficacy of olaparib when given in combination with abiraterone was assessed by rPFS, defined as the time from randomisation to disease progression using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 (for soft tissue disease) and Prostate Cancer Working Group 2 (PCWG-2) (for bone disease) criteria, or death. Progression using RECIST 1.1 criteria was defined as at least 20% increase from baseline in the sum of diameters of target lesions, progression of existing non-target lesions, or the appearance of at least 1 new lesion. Progression using PCWG-2 criteria was determined if 2 or more new metastatic bone lesions were observed (with a total of at least 4 new lesions since baseline assessment if observed at the 12 week scan, or persistence of or increase in number of lesions if observed after the 12 week scan as determined by a confirmatory scan at least 6 weeks later or at next scheduled visit).
Time Frame	From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Median (95% Confidence Interval); Unit of Measure: Months
	13.8; (10.8 to 20.4)	8.2; (5.5 to 9.7)

4. Primary Outcome

Title	Part B: Percentage of Patients With Progression Events or Death (rPFS)
Description	The efficacy of olaparib when given in combination with abiraterone was assessed by rPFS, defined as the time from randomisation to disease progression using RECIST version 1.1 (for soft tissue disease) and PCWG-2 (for bone disease) criteria, or death. Progression using RECIST 1.1 criteria was defined as at least 20% increase from baseline in the sum of diameters of target lesions, progression of existing non-target lesions, or the appearance of at least 1 new lesion. Progression using PCWG-2 criteria was determined if 2 or more new metastatic bone lesions were observed (with a total of at least 4 new lesions since baseline assessment if observed at the 12 week scan, or persistence of or increase in number of lesions if observed after the 12 week scan as determined by a confirmatory scan at least 6 weeks later or at next scheduled visit). The percentage of patients with progression events is presented overall and according to RECIST 1.1 and/or PCWG-2 criteria, or death.
Time Frame	From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Measure Type: Number; Unit of Measure: Percentage of patients
	64.8	76.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Olaparib + Abiraterone, Part B: Placebo + Abiraterone
	Comments	The 1-sided p-value provides a test for rejecting the null hypothesis of no treatment effect versus the superiority alternative that patients on olaparib have a lower risk of progression compared with placebo.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.017
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.651
	Confidence Interval	(2-Sided) 95%; 0.438 to 0.969
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Part A Pharmacokinetics (PK): Olaparib Maximum Plasma Concentration at Steady State (Cmax,ss)
Description	Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib Cmax,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.
Time Frame	PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Arm/Group Title		Part A Cohort 2 Group 1: Olaparib, Olaparib + Abiraterone	Part A Cohort 2 Group 2: Abiraterone, Olaparib + Abiraterone
Arm/Group Description:		Patients received olaparib 300 mg bid alone for 3 to 7 days to determine the steady state PK profile for olaparib. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received abiraterone 1000 mg once daily alone for 5 to 7 days to determine the steady state PK profile for abiraterone. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed		7	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: micrograms per millilitre (mcg/mL)
Olaparib alone	Number Analyzed	6 participants	0 participants
		7.781; (25.06%)
Olaparib + abiraterone	Number Analyzed	5 participants	6 participants
		6.504; (20.90%)	7.724; (28.05%)

6. Secondary Outcome

Title	Part A PK: Abiraterone Cmax,ss
Description	Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone Cmax,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.
Time Frame	PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Arm/Group Title		Part A Cohort 2 Group 1: Olaparib, Olaparib + Abiraterone	Part A Cohort 2 Group 2: Abiraterone, Olaparib + Abiraterone
Arm/Group Description:		Patients received olaparib 300 mg bid alone for 3 to 7 days to determine the steady state PK profile for olaparib. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received abiraterone 1000 mg once daily alone for 5 to 7 days to determine the steady state PK profile for abiraterone. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed		7	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms per millilitre (ng/mL)
Abiraterone alone	Number Analyzed	0 participants	6 participants
			145.8; (135.5%)
Olaparib + abiraterone	Number Analyzed	6 participants	4 participants
		130.7; (68.87%)	86.12; (48.88%)

7. Secondary Outcome

Title	Part A PK Analysis: Olaparib Time to Reach Maximum Plasma Concentration at Steady State (Tmax,ss)
Description	Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib tmax,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.
Time Frame	PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Arm/Group Title		Part A Cohort 2 Group 1: Olaparib, Olaparib + Abiraterone	Part A Cohort 2 Group 2: Abiraterone, Olaparib + Abiraterone
Arm/Group Description:		Patients received olaparib 300 mg bid alone for 3 to 7 days to determine the steady state PK profile for olaparib. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received abiraterone 1000 mg once daily alone for 5 to 7 days to determine the steady state PK profile for abiraterone. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed		7	6
Median (Full Range); Unit of Measure: Hours (h)
Olaparib alone	Number Analyzed	6 participants	0 participants
		2.000; (1.00 to 2.17)
Olaparib + abiraterone	Number Analyzed	5 participants	6 participants
		2.080; (2.00 to 4.00)	2.000; (0.500 to 3.02)

8. Secondary Outcome

Title	Part A PK: Abiraterone Tmax,ss
Description	Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone tmax,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.
Time Frame	PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Arm/Group Title		Part A Cohort 2 Group 1: Olaparib, Olaparib + Abiraterone	Part A Cohort 2 Group 2: Abiraterone, Olaparib + Abiraterone
Arm/Group Description:		Patients received olaparib 300 mg bid alone for 3 to 7 days to determine the steady state PK profile for olaparib. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received abiraterone 1000 mg once daily alone for 5 to 7 days to determine the steady state PK profile for abiraterone. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed		7	6
Median (Full Range); Unit of Measure: Hours
Abiraterone alone	Number Analyzed	0 participants	6 participants
			2.525; (1.00 to 3.00)
Olaparib + abiraterone	Number Analyzed	6 participants	4 participants
		3.000; (1.08 to 3.00)	2.500; (2.00 to 3.02)

9. Secondary Outcome

Title	Part A PK Analysis: Olaparib Minimum Plasma Concentration at Steady State (Cmin,ss)
Description	Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib Cmin,ss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.
Time Frame	PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Arm/Group Title		Part A Cohort 2 Group 1: Olaparib, Olaparib + Abiraterone	Part A Cohort 2 Group 2: Abiraterone, Olaparib + Abiraterone
Arm/Group Description:		Patients received olaparib 300 mg bid alone for 3 to 7 days to determine the steady state PK profile for olaparib. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received abiraterone 1000 mg once daily alone for 5 to 7 days to determine the steady state PK profile for abiraterone. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed		7	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg/mL
Olaparib alone	Number Analyzed	6 participants	0 participants
		1.264; (46.58%)
Olaparib + abiraterone	Number Analyzed	5 participants	6 participants
		0.9170; (31.56%)	1.279; (65.36%)

10. Secondary Outcome

Title	Part A PK: Abiraterone Cmin,ss
Description	Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone Cmin,ss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.
Time Frame	PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Arm/Group Title		Part A Cohort 2 Group 1: Olaparib, Olaparib + Abiraterone	Part A Cohort 2 Group 2: Abiraterone, Olaparib + Abiraterone
Arm/Group Description:		Patients received olaparib 300 mg bid alone for 3 to 7 days to determine the steady state PK profile for olaparib. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received abiraterone 1000 mg once daily alone for 5 to 7 days to determine the steady state PK profile for abiraterone. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed		7	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Abiraterone alone	Number Analyzed	0 participants	6 participants
			8.376; (96.52%)
Olaparib + abiraterone	Number Analyzed	6 participants	4 participants
		7.983; (163.3%)	6.358; (50.96%)

11. Secondary Outcome

Title	Part A PK Analysis: Olaparib Area Under the Plasma Concentration-Time Curve at Steady State (AUCss)
Description	Following multiple dosing to steady state of olaparib 300 mg bid, the Cohort 2 olaparib AUCss is presented for olaparib monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.
Time Frame	PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Arm/Group Title		Part A Cohort 2 Group 1: Olaparib, Olaparib + Abiraterone	Part A Cohort 2 Group 2: Abiraterone, Olaparib + Abiraterone
Arm/Group Description:		Patients received olaparib 300 mg bid alone for 3 to 7 days to determine the steady state PK profile for olaparib. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received abiraterone 1000 mg once daily alone for 5 to 7 days to determine the steady state PK profile for abiraterone. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed		7	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg*h/mL
Olaparib alone	Number Analyzed	6 participants	0 participants
		45.27; (31.89%)
Olaparib + abiraterone	Number Analyzed	5 participants	6 participants
		40.83; (11.47%)	49.51; (37.30%)

12. Secondary Outcome

Title	Part A PK: Abiraterone AUCss
Description	Following multiple dosing to steady state of abiraterone 1000 mg once daily, the Cohort 2 abiraterone AUCss is presented for abiraterone monotherapy and for olaparib given in combination with abiraterone. Only patients with data available for analysis at each time point are presented.
Time Frame	PK sampling for Cohort 2 Group 1 was between Days 3 and 7 for olaparib, and Days 4 and 8 for olaparib and abiraterone. PK sampling for Cohort 2 Group 2 was between Days 5 and 7 for abiraterone, and Days 6 and 8 for olaparib and abiraterone.

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all patients who received at least 1 dose of olaparib per the protocol, for whom there was at least 1 reportable PK concentration and who had no important protocol deviations or AEs that impacted on PK on all PK sampling days. Only patients with data available for analysis at each time point are presented.

Arm/Group Title		Part A Cohort 2 Group 1: Olaparib, Olaparib + Abiraterone	Part A Cohort 2 Group 2: Abiraterone, Olaparib + Abiraterone
Arm/Group Description:		Patients received olaparib 300 mg bid alone for 3 to 7 days to determine the steady state PK profile for olaparib. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received abiraterone 1000 mg once daily alone for 5 to 7 days to determine the steady state PK profile for abiraterone. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days to determine the PK profiles of both olaparib and abiraterone. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed		7	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
Abiraterone alone	Number Analyzed	0 participants	6 participants
			825.5; (105.5%)
Olaparib + abiraterone	Number Analyzed	6 participants	4 participants
		718.9; (102.0%)	524.6; (37.65%)

13. Secondary Outcome

Title	Part B: Percentage of Patients Experiencing AEs
Description	The safety and tolerability of olaparib when given in combination with abiraterone was assessed during Part B of the study. The percentage of patients experiencing AEs, including information on seriousness, severity, study treatment relationship and those leading to discontinuation for all doses of olaparib and for abiraterone are presented. Severity of AEs was assessed using the NCI Common Terminology CTCAE v4.0. AEs were assigned to a Grade from 1 through 5 as follows: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening requiring hospitalisation; Grade 4: Life-threatening consequences; Grade 5: Death related to AE. 'c-r' = causally related. 'discont' = discontinuation. 'ola/pla' = olaparib/placebo.
Time Frame	From first dose of study treatment following randomisation in Part B up to 30 days following last dose of study treatment (up to approximately 3 years).

Outcome Measure Data

Analysis Population Description

Part B safety analysis set consisted of all patients randomised into Part B of the study who received at least 1 dose of olaparib/placebo.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Measure Type: Number; Unit of Measure: Percentage of patients
Any AE c-r to ola/pla + abiraterone	45.1	12.7
Any AE c-r to ola/pla only	18.3	9.9
Any AE c-r to abiraterone only	1.4	7.0
Any AE CTCAE Grade 3 or higher	53.5	28.2
Any AE CTCAE Grade 3 or higher c-r to ola/pla	23.9	5.6
Any AE CTCAE Grade 3 or higher c-r to abiraterone	16.9	1.4
Any AE with outcome = death	5.6	1.4
Any AE with outcome = death c-r to ola/pla	1.4	0
Any AE with outcome = death c-r to abiraterone	0	0
Any SAE	35.2	19.7
Any SAE c-r to ola/pla	9.9	1.4
Any SAE c-r to abiraterone	5.6	0
Any AE causing discont of ola/pla	29.6	9.9
Any AE causing discont of treatment c-r to ola/pla	16.9	5.6
Any AE causing discont treatment c-r abiraterone	8.5	1.4

14. Secondary Outcome

Title	Part B: Median Best Percentage Change From Baseline in Prostate Specific Antigen (PSA) Levels
Description	The best percentage change from baseline in PSA levels was determined to assess the anti-tumour activity of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone. The best percentage change was defined as the biggest reduction in PSA level compared with baseline or smallest increase in the absence of a decrease.
Time Frame	From baseline, then every 4 weeks up to Week 52, and then every 12 weeks.

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. Only patients with data available for analysis are presented.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Median (Full Range); Unit of Measure: Percentage change in PSA level
	-54.16; (-100.0 to 533.2)	-49.85; (-100.0 to 230.1)

15. Secondary Outcome

Title	Part B: Percentage of Patients With PSA Responses
Description	The percentages of patients with single visit responses and with confirmed responses are presented to assess the anti-tumour activity of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone. A single visit response was defined as any post-dose visit PSA level reduced by 50% or more compared with baseline. A confirmed response was defined as a reduction in PSA level of 50% or more on 2 consecutive occasions at least 4 weeks apart compared with baseline. Patients may have had more than 1 single visit response or confirmed response but were counted once.
Time Frame	From baseline, then every 4 weeks up to Week 24, and then every 12 weeks.

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Measure Type: Number; Number (80% Confidence Interval); Unit of Measure: Percentage of patients
Single visit response	50.7; (43.10 to 58.31)	47.9; (40.29 to 55.49)
Confirmed response	47.9; (40.29 to 55.49)	42.3; (34.74 to 49.77)

16. Secondary Outcome

Title	Part B: Median Best Percentage Change From Baseline in Circulating Tumour Cell (CTC) Level
Description	The median best percentage change from baseline in CTC levels was determined to assess the anti-tumour activity of olaparib when given in combination with abiraterone, compared with placebo given in addition to abiraterone. The best percentage change was defined as the biggest CTC level reduction compared with baseline or smallest increase in the absence of a decrease.
Time Frame	From baseline, then every 4 weeks up to Week 24, and then every 12 weeks.

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. Only patients with data available for analysis are presented.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Median (Full Range); Unit of Measure: Percentage change in CTC level
	-1.0; (-478 to 613)	-1.0; (-1279 to 414)

17. Secondary Outcome

Title	Part B: Percentage of Patients With at Least One Objective Response (Objective Response Rate [ORR])
Description	The overall radiological ORR was calculated to assess the anti-tumour activity of olaparib in combination with abiraterone, compared with placebo in combination with abiraterone. The best overall ORR was defined as the percentage of patients with at least 1 visit response of complete response (CR) or partial response (PR) in soft tissue disease assessed by RECIST 1.1 and also bone scan status of non-progressive disease or non-evaluable for their bone scans assessed by PCWG-2. CR: Disappearance of all target lesions. Reduction of pathological lymph nodes to <10 millimetres. PR: At least a 30% decrease in the sum of diameters of target lesions from baseline. The percentage of patients with a response is presented.
Time Frame	From baseline, then every 4 weeks up to Week 52, and then every 12 weeks.

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. Only patients with data available for analysis are presented. Only patients with measurable disease at baseline are included.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Measure Type: Number; Unit of Measure: Percentage of patients
	27.3	31.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Olaparib + Abiraterone, Part B: Placebo + Abiraterone
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.309
	Comments	The p value was calculated with a 1-sided significance level of 2.5%.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.813
	Confidence Interval	(2-Sided) 95%; 0.285 to 2.261
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Median Time to First Subsequent Therapy (TFST) and Median Time to Second Subsequent Therapy (TSST)
Description	The TFST and TSST were determined to assess the anti-tumour activity of olaparib when given in combination with abiraterone, compared with placebo given in addition to abiraterone. TFST was defined as the time from randomisation to the earlier of first subsequent anti-cancer therapy start date following study treatment discontinuation, or death. TSST was defined as the time from randomisation to the earlier of the second subsequent anti-cancer therapy start date following study treatment discontinuation, or death.
Time Frame	From randomisation until analysis cut-off date (up to approximately 3 years).

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Median (95% Confidence Interval); Unit of Measure: Months
TFST	13.5; (11.1 to 17.2)	9.7; (7.3 to 12.9)
TSST	19.6; (16.5 to 25.1)	18.0; (16.9 to 20.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Olaparib + Abiraterone, Part B: Placebo + Abiraterone
	Comments	Olapatib + abiraterone versus placebo + abiraterone: TFST
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.095
	Comments	The p value was calculated with a 1-sided significance level of 2.5%.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.781
	Confidence Interval	(2-Sided) 95%; 0.540 to 1.130
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part B: Olaparib + Abiraterone, Part B: Placebo + Abiraterone
	Comments	Olaparib + abiraterone versus placebo + abiraterone: TSST
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.147
	Comments	The p value was calculated with a 1-sided significance level of 2.5%.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.809
	Confidence Interval	(2-Sided) 95%; 0.545 to 1.201
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Part B: Median Overall Survival (OS)
Description	OS was determined to assess the efficacy of olaparib when given in addition to abiraterone, compared with placebo given in addition to abiraterone. OS was performed at the time of the analysis of rPFS, and the median OS, calculated using the Kaplan-Meier technique, is presented.
Time Frame	From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months.

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Median (95% Confidence Interval); Unit of Measure: Months
	22.7; (17.4 to 29.4)	20.9; (17.6 to 26.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Olaparib + Abiraterone, Part B: Placebo + Abiraterone
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.331
	Comments	The p value was calculated with a 1-sided significance level of 2.5%.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.911
	Confidence Interval	(2-Sided) 95%; 0.600 to 1.384
	Estimation Comments	[Not Specified]

20. Secondary Outcome

Title	Part B: Median Time to Second Progression or Death (PFS2)
Description	The efficacy of olaparib when given in combination with abiraterone was assessed by PFS2, defined by local standard clinical practice and included objective radiological progression by RECIST 1.1 (soft tissue), symptomatic progression, rise in PSA level or death in the absence of overall progression.
Time Frame	From randomisation until analysis cut-off date (up to approximately 3 years).

Outcome Measure Data

Analysis Population Description

The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received.

Arm/Group Title	Part B: Olaparib + Abiraterone	Part B: Placebo + Abiraterone
Arm/Group Description:	Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.	Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
Overall Number of Participants Analyzed	71	71
Median (95% Confidence Interval); Unit of Measure: Months
	23.3 [1]; (17.4 to NA)	18.5; (16.1 to 23.8)

[1]

Insufficient number of patients with events to allow calculation of upper limit for 95% confidence interval.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Olaparib + Abiraterone, Part B: Placebo + Abiraterone
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.140
	Comments	The p value was calculated with a 1-sided significance level of 2.5%.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.788
	Confidence Interval	(2-Sided) 95%; 0.511 to 1.215
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Part A: From baseline (Day 1 for each cohort) up to 30 days following last dose of study treatment. Part B: From first dose of study treatment following randomisation up to 30 days following last dose of study treatment (up to approximately 3 years).
Adverse Event Reporting Description	The Part A Safety analysis set consisted of all patients who received at least 1 dose of study treatment in Part A. Part B safety analysis set consisted of all patients randomised into Part B of the study who received at least 1 dose of olaparib/placebo.
Arm/Group Title	Part A Cohort 1: Olaparib 200 mg + Abiraterone		Part A Cohort 2: Olaparib 300 mg + Abiraterone		Part B: Olaparib + Abiraterone		Part B: Placebo + Abiraterone
Arm/Group Description	Patients received olaparib 200 mg bid and abiraterone 1000 mg once daily. Patients were assessed at Weeks 1, 2 and 4, then every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.		If the combination of olaparib 200 mg + abiraterone 1000 mg was well tolerated (determined after a minimum of 14 days treatment in Cohort 1), patients were recruited into Cohort 2. Cohort 2 Group 1: patients received olaparib 300 mg bid alone for 3 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 5 days. Cohort 2 Group 2: patients received abiraterone 1000 mg once daily alone for 5 to 7 days. Patients then received olaparib 300 mg bid and abiraterone 1000 mg once daily for at least 3 days. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.		Patients received the selected dose of olaparib 300 mg bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.		Patients received placebo bid + abiraterone 1000 mg once daily. Patients were assessed every 4 weeks up to Week 52, and every 12 weeks thereafter. Patients also received prednisone or prednisolone 5 mg bid in combination with the abiraterone treatment.
All-Cause Mortality
	Part A Cohort 1: Olaparib 200 mg + Abiraterone		Part A Cohort 2: Olaparib 300 mg + Abiraterone		Part B: Olaparib + Abiraterone		Part B: Placebo + Abiraterone
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/3 (0.00%)		1/13 (7.69%)		43/71 (60.56%)		45/71 (63.38%)
Serious Adverse Events
	Part A Cohort 1: Olaparib 200 mg + Abiraterone		Part A Cohort 2: Olaparib 300 mg + Abiraterone		Part B: Olaparib + Abiraterone		Part B: Placebo + Abiraterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.67%)		3/13 (23.08%)		25/71 (35.21%)		14/71 (19.72%)
Blood and lymphatic system disorders
Anaemia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	5/71 (7.04%)	7	1/71 (1.41%)	1
Febrile neutropenia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Cardiac disorders
Acute myocardial infarction † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	2/71 (2.82%)	2	0/71 (0.00%)	0
Cardiac failure † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Cardiac failure chronic † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Myocardial infarction † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	2/71 (2.82%)	2	0/71 (0.00%)	0
Eye disorders
Eye haemorrhage † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Gastrointestinal disorders
Constipation † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Intestinal obstruction † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Nausea † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Proctitis † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Vomiting † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
General disorders
General physical health deterioration † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Pyrexia † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Infections and infestations
Bacteraemia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	2/71 (2.82%)	2	0/71 (0.00%)	0
Bacterial infection † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Candida infection † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Cellulitis † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Gastroenteritis † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Influenza † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Mediastinitis † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Pneumonia † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	4/71 (5.63%)	4	3/71 (4.23%)	3
Pyelonephritis chronic † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Respiratory tract infection † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Sepsis † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Septic shock † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Urinary tract infection † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	2/71 (2.82%)	3	2/71 (2.82%)	2
Injury, poisoning and procedural complications
Humerus fracture † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Patella fracture † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Spinal fracture † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Subdural haematoma † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Urinary tract stoma complication † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Metabolism and nutrition disorders
Dehydration † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Hypokalaemia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the tongue † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Nervous system disorders
Cognitive disorder † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Ischaemic stroke † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Thrombotic stroke † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Renal and urinary disorders
Renal failure † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Interstitial lung disease † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Pneumonitis † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Respiratory failure † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	2/71 (2.82%)	2	0/71 (0.00%)	0
Vascular disorders
Internal haemorrhage † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Peripheral ischaemia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Thrombosis † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part A Cohort 1: Olaparib 200 mg + Abiraterone		Part A Cohort 2: Olaparib 300 mg + Abiraterone		Part B: Olaparib + Abiraterone		Part B: Placebo + Abiraterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100.00%)		7/13 (53.85%)		63/71 (88.73%)		52/71 (73.24%)
Blood and lymphatic system disorders
Anaemia † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	18/71 (25.35%)	23	1/71 (1.41%)	1
Lymphopenia † 1	0/3 (0.00%)	0	1/13 (7.69%)	2	1/71 (1.41%)	1	0/71 (0.00%)	0
Neutropenia † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	8/71 (11.27%)	8	0/71 (0.00%)	0
Cardiac disorders
Arrhythmia † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Ear and labyrinth disorders
Cerumen impaction † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Tympanic membrane perforation † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Eye disorders
Eyelid oedema † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	4/71 (5.63%)	5	0/71 (0.00%)	0
Ocular hyperaemia † 1	1/3 (33.33%)	1	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Gastrointestinal disorders
Abdominal discomfort † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Abdominal pain † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	8/71 (11.27%)	9	1/71 (1.41%)	1
Abdominal pain upper † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	1/71 (1.41%)	1	1/71 (1.41%)	1
Constipation † 1	1/3 (33.33%)	1	2/13 (15.38%)	2	17/71 (23.94%)	19	8/71 (11.27%)	10
Diarrhoea † 1	2/3 (66.67%)	4	3/13 (23.08%)	3	11/71 (15.49%)	17	8/71 (11.27%)	11
Dyspepsia † 1	1/3 (33.33%)	1	1/13 (7.69%)	1	0/71 (0.00%)	0	3/71 (4.23%)	3
Dysphagia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	5/71 (7.04%)	5	2/71 (2.82%)	2
Frequent bowel movements † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Gastrooesophageal reflux disease † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	4/71 (5.63%)	4	0/71 (0.00%)	0
Nausea † 1	2/3 (66.67%)	5	2/13 (15.38%)	2	27/71 (38.03%)	42	15/71 (21.13%)	16
Rectal haemorrhage † 1	2/3 (66.67%)	2	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Vomiting † 1	1/3 (33.33%)	4	2/13 (15.38%)	3	14/71 (19.72%)	26	9/71 (12.68%)	12
General disorders
Asthenia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	16/71 (22.54%)	22	10/71 (14.08%)	11
Fatigue † 1	1/3 (33.33%)	1	1/13 (7.69%)	1	15/71 (21.13%)	16	9/71 (12.68%)	11
Oedema peripheral † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	14/71 (19.72%)	16	8/71 (11.27%)	8
Peripheral swelling † 1	0/3 (0.00%)	0	2/13 (15.38%)	3	3/71 (4.23%)	3	1/71 (1.41%)	1
Pyrexia † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	10/71 (14.08%)	11	1/71 (1.41%)	1
Infections and infestations
Arthritis infective † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Cellulitis † 1	0/3 (0.00%)	0	1/13 (7.69%)	3	0/71 (0.00%)	0	0/71 (0.00%)	0
Furuncle † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Gastroenteritis † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	4/71 (5.63%)	4	1/71 (1.41%)	1
Lower respiratory tract infection † 1	2/3 (66.67%)	2	0/13 (0.00%)	0	0/71 (0.00%)	0	3/71 (4.23%)	3
Oral candidiasis † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	2/71 (2.82%)	2	1/71 (1.41%)	2
Sepsis † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Sinusitis † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	1/71 (1.41%)	2	1/71 (1.41%)	1
Urinary tract infection † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	8/71 (11.27%)	9	2/71 (2.82%)	2
Viral upper respiratory tract infection † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	8/71 (11.27%)	10	3/71 (4.23%)	3
Injury, poisoning and procedural complications
Contusion † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	3/71 (4.23%)	3	2/71 (2.82%)	2
Fall † 1	2/3 (66.67%)	2	1/13 (7.69%)	1	5/71 (7.04%)	5	1/71 (1.41%)	2
Humerus fracture † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Laceration † 1	1/3 (33.33%)	2	1/13 (7.69%)	1	1/71 (1.41%)	1	0/71 (0.00%)	0
Lower limb fracture † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Rib fracture † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	1/71 (1.41%)	1
Thermal burn † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Wound secretion † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	1/71 (1.41%)	1	1/71 (1.41%)	1
Aspartate aminotransferase increased † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	1/71 (1.41%)	1	1/71 (1.41%)	1
Blood calcium decreased † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Blood creatinine increased † 1	1/3 (33.33%)	3	1/13 (7.69%)	1	3/71 (4.23%)	3	1/71 (1.41%)	1
Blood glucose increased † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Blood potassium decreased † 1	1/3 (33.33%)	1	1/13 (7.69%)	2	2/71 (2.82%)	3	1/71 (1.41%)	2
Blood urea increased † 1	1/3 (33.33%)	3	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Body temperature increased † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	1/71 (1.41%)	1
Electrocardiogram QT prolonged † 1	0/3 (0.00%)	0	1/13 (7.69%)	2	0/71 (0.00%)	0	0/71 (0.00%)	0
Haemoglobin decreased † 1	0/3 (0.00%)	0	1/13 (7.69%)	2	0/71 (0.00%)	0	0/71 (0.00%)	0
Heart rate irregular † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Urine output increased † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Weight decreased † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	4/71 (5.63%)	4	4/71 (5.63%)	4
Metabolism and nutrition disorders
Decreased appetite † 1	1/3 (33.33%)	1	1/13 (7.69%)	1	12/71 (16.90%)	12	5/71 (7.04%)	5
Fluid retention † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Hyperglycaemia † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	1/71 (1.41%)	1	1/71 (1.41%)	2
Hypocalcaemia † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	1/71 (1.41%)	1	2/71 (2.82%)	2
Hypokalaemia † 1	1/3 (33.33%)	3	1/13 (7.69%)	3	5/71 (7.04%)	7	4/71 (5.63%)	6
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/3 (33.33%)	1	1/13 (7.69%)	1	8/71 (11.27%)	8	4/71 (5.63%)	4
Back pain † 1	3/3 (100.00%)	5	1/13 (7.69%)	1	17/71 (23.94%)	21	14/71 (19.72%)	18
Bone pain † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	11/71 (15.49%)	12	9/71 (12.68%)	9
Groin pain † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	1/71 (1.41%)	1	0/71 (0.00%)	0
Joint swelling † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	1/71 (1.41%)	1
Muscle spasms † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	4/71 (5.63%)	4	2/71 (2.82%)	2
Musculoskeletal chest pain † 1	2/3 (66.67%)	4	0/13 (0.00%)	0	1/71 (1.41%)	1	5/71 (7.04%)	7
Musculoskeletal pain † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	7/71 (9.86%)	8	6/71 (8.45%)	7
Neck pain † 1	0/3 (0.00%)	0	2/13 (15.38%)	2	2/71 (2.82%)	2	3/71 (4.23%)	3
Osteopenia † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Osteoporosis † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Pain in extremity † 1	1/3 (33.33%)	2	2/13 (15.38%)	3	5/71 (7.04%)	6	4/71 (5.63%)	4
Spinal pain † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	2/71 (2.82%)	2	3/71 (4.23%)	3
Nervous system disorders
Dizziness † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	4/71 (5.63%)	5	2/71 (2.82%)	2
Dysgeusia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	4/71 (5.63%)	5	2/71 (2.82%)	2
Headache † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	6/71 (8.45%)	9	5/71 (7.04%)	7
Paraesthesia † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	1/71 (1.41%)	1	1/71 (1.41%)	1
Tremor † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Psychiatric disorders
Affect lability † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Depressed mood † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Depression † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	2/71 (2.82%)	2	1/71 (1.41%)	1
Euphoric mood † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Insomnia † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	6/71 (8.45%)	7	2/71 (2.82%)	2
Renal and urinary disorders
Hypertonic bladder † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Pollakiuria † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	1/71 (1.41%)	1
Urinary retention † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	2/71 (2.82%)	2	1/71 (1.41%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/3 (0.00%)	0	1/13 (7.69%)	2	11/71 (15.49%)	17	2/71 (2.82%)	2
Dyspnoea † 1	1/3 (33.33%)	2	1/13 (7.69%)	1	10/71 (14.08%)	12	4/71 (5.63%)	4
Nasal congestion † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Pneumonitis † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	1/71 (1.41%)	1	0/71 (0.00%)	0
Pulmonary embolism † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	2/71 (2.82%)	2	1/71 (1.41%)	1
Skin and subcutaneous tissue disorders
Blister † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Dry skin † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	1/71 (1.41%)	1
Purpura † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	2/71 (2.82%)	2	0/71 (0.00%)	0
Rash † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	1/71 (1.41%)	1	1/71 (1.41%)	1
Skin atrophy † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	0/71 (0.00%)	0
Skin lesion † 1	1/3 (33.33%)	1	0/13 (0.00%)	0	0/71 (0.00%)	0	0/71 (0.00%)	0
Skin ulcer † 1	0/3 (0.00%)	0	1/13 (7.69%)	1	0/71 (0.00%)	0	1/71 (1.41%)	1
Vascular disorders
Haematoma † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	4/71 (5.63%)	5	0/71 (0.00%)	0
Hot flush † 1	1/3 (33.33%)	1	1/13 (7.69%)	1	3/71 (4.23%)	3	2/71 (2.82%)	2
Hypertension † 1	0/3 (0.00%)	0	0/13 (0.00%)	0	3/71 (4.23%)	3	4/71 (5.63%)	5
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by 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.

Results Point of Contact

• Name/Title: Medical Director
• Organization: AstraZeneca
• Phone: +13028851180
• EMail: ClinicalTrialTransparency@astrazeneca.com

Publications:

Clarke N, Wiechno P, Alekseev B, Sala N, Jones R, Kocak I, Chiuri VE, Jassem J, Flechon A, Redfern C, Goessl C, Burgents J, Kozarski R, Hodgson D, Learoyd M, Saad F. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):975-986. doi: 10.1016/S1470-2045(18)30365-6. Epub 2018 Jun 4.

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

Saad F, Thiery-Vuillemin A, Wiechno P, Alekseev B, Sala N, Jones R, Kocak I, Chiuri VE, Jassem J, Flechon A, Redfern C, Kang J, Burgents J, Gresty C, Degboe A, Clarke NW. Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration-resistant prostate cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2022 Oct;23(10):1297-1307. doi: 10.1016/S1470-2045(22)00498-3. Epub 2022 Sep 2. Erratum In: Lancet Oncol. 2022 Oct;23(10):e446.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01972217
• Other Study ID Numbers: D081DC00008; UVA97934 ( Other Identifier: Quintiles ); 2013-003520-37 ( EudraCT Number )
• First Submitted: October 24, 2013
• First Posted: October 30, 2013
• Results First Submitted: September 6, 2018
• Results First Posted: October 2, 2018
• Last Update Posted: November 14, 2023