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

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ClinicalTrials.gov Identifier: NCT01972217
Recruitment Status : Active, not recruiting
First Posted : October 30, 2013
Results First Posted : October 2, 2018
Last Update Posted : October 7, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
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
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
Hide 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.
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
Hide 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
Hide 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%
1.Primary Outcome
Title Part A: Percentage of Patients Experiencing Adverse Events (AEs)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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).
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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])
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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)
Hide 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).
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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)
Hide 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).
Hide Outcome Measure Data
Hide 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
Hide 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.
Show Statistical Analysis 1 Hide 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]
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
Hide 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%)    
Show Serious Adverse Events Hide 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
Show Other (Not Including Serious) Adverse Events Hide 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
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
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: AstraZeneca
Phone: +13028851180
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01972217     History of Changes
Other Study ID Numbers: D081DC00008
UVA97934 ( Other Identifier: Quintiles )
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: October 7, 2019