Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| UVA97934 | Other Identifier | Quintiles | |
| 2013-003520-37 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a 2-part study in patients with metastatic CRPC. Part A is an open-label safety run-in study to assess the safety, tolerability and pharmacokinetics (PK) of olaparib when given in addition to abiraterone 1000 mg once daily. Part B is a randomised, double-blind, placebo controlled comparison of the efficacy, safety and tolerability of the dose of olaparib selected from Part A when given in addition to abiraterone, versus placebo given in addition to abiraterone. Abiraterone is indicated in combination with prednisone or prednisolone for the treatment of patients with metastatic CRPC. Prednisone or prednisolone 5 mg twice daily (bid) will be administered with the abiraterone in this study.
This is a 2-part study in patients with metastatic CRPC. Part A is an open-label safety run-in study to assess the safety, tolerability and PK of olaparib when given in addition to abiraterone 1000 mg once daily. Part B is a randomised, double-blind, placebo-controlled comparison of the efficacy, safety and tolerability of the dose of olaparib selected from Part A when given in addition to abiraterone, versus placebo in addition to abiraterone.
Abiraterone is indicated in combination with prednisone or prednisolone for the treatment of patients with metastatic CRPC. Prednisone or prednisolone 5 mg bid will be administered with the abiraterone in this study, but throughout this protocol the treatment will be referred to simply as abiraterone.
For Part A of the study, 15 to 18 evaluable patients (Cohorts 1 and 2) are planned to be enrolled from approximately 4 sites in approximately 1 or 2 countries, and a further 12 patients may be recruited into a 3rd cohort if necessary.
For Part B of the study, approximately 140 patients who have received prior chemotherapy containing docetaxel will be randomised from approximately 40 sites in North America and Europe. Patients who have been dosed in Part A of the study may not participate in Part B.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Olaparib | Active Comparator | 200 mg or 300 mg bid |
|
| Placebo | Placebo Comparator | placebo to match olaparib bid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Olaparib | Drug | Olaparib bid |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Percentage of Patients Experiencing Adverse Events (AEs) | 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. | Cohort 1 and 2: From baseline in Part A (Day 1 for each cohort) up to 30 days following last dose of study treatment. |
| Part A: Number of Patients With Dose Limiting Toxicities (DLTs) | 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. | From Day 1 for Cohort 1 and from Day 4 for Cohort 2 up to 14 days treatment with olaparib + abiraterone for 3 patients. |
| Part B: Median Radiological Progression-Free Survival (rPFS) Time | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Part A Pharmacokinetics (PK): Olaparib Maximum Plasma Concentration at Steady State (Cmax,ss) | 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. | 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. |
Not provided
Inclusion Criteria:
Provide informed consent for the pharmacogenetic sampling and analyses.
Exclusion Criteria:
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, its agents and/or staff at the study site).
Previous treatment in the present study.
Treatment with any of the following:
With the exception of alopecia or toxicities related to the use of gonadotropinreleasing hormone agonists, any unresolved toxicities from prior therapy greater than CTCAE Grade 2 at the time of starting study treatment.
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment.
As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
Any of the following cardiac criteria:
Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years.
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of olaparib or abiraterone.
History of hypersensitivity to active or inactive excipients of olaparib or abiraterone or drugs with a similar chemical structure or class to olaparib or abiraterone.
Patients with myelodysplastic syndrome/acute myeloid leukaemia.
Current disease or condition known to interfere with absorption, distribution, metabolism, or excretion of drugs, at the Investigator's discretion.
Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
Exclusion from the genetic research may be for any of the exclusion criteria specified in the main study or any of the following:
Previous allogeneic bone marrow transplant.
Non-leukocyte depleted whole blood transfusion within 120 days of the date of the pharmacogenetic sample collection.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | San Diego | California | 92123 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29880291 | Background | 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. | |
| 36063830 |
| Label | URL |
|---|---|
| Redacted SAP | View source |
Not provided
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Part A Cohort 1: Olaparib 200 mg + Abiraterone | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A: Open-label Safety Run-in Period |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 20, 2015 | Sep 6, 2018 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo bid |
|
|
| Abiraterone | Drug | Abiraterone 1000 mg |
|
| Prednisone or prednisolone | Drug | Prednisone or prednisolone 5 mg bid will be co-administered with the abiraterone in this study. |
|
| From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months. |
| Part B: Percentage of Patients With Progression Events or Death (rPFS) | 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. | From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months. |
| Part A PK: Abiraterone Cmax,ss | 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. | 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. |
| Part A PK Analysis: Olaparib Time to Reach Maximum Plasma Concentration at Steady State (Tmax,ss) | 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. | 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. |
| Part A PK: Abiraterone Tmax,ss | 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. | 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. |
| Part A PK Analysis: Olaparib Minimum Plasma Concentration at Steady State (Cmin,ss) | 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. | 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. |
| Part A PK: Abiraterone Cmin,ss | 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. | 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. |
| Part A PK Analysis: Olaparib Area Under the Plasma Concentration-Time Curve at Steady State (AUCss) | 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. | 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. |
| Part A PK: Abiraterone AUCss | 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. | 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. |
| Part B: Percentage of Patients Experiencing AEs | 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. | 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). |
| Part B: Median Best Percentage Change From Baseline in Prostate Specific Antigen (PSA) Levels | 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. | From baseline, then every 4 weeks up to Week 52, and then every 12 weeks. |
| Part B: Percentage of Patients With PSA Responses | 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. | From baseline, then every 4 weeks up to Week 24, and then every 12 weeks. |
| Part B: Median Best Percentage Change From Baseline in Circulating Tumour Cell (CTC) Level | 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. | From baseline, then every 4 weeks up to Week 24, and then every 12 weeks. |
| Part B: Percentage of Patients With at Least One Objective Response (Objective Response Rate [ORR]) | 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. | From baseline, then every 4 weeks up to Week 52, and then every 12 weeks. |
| Median Time to First Subsequent Therapy (TFST) and Median Time to Second Subsequent Therapy (TSST) | 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. | From randomisation until analysis cut-off date (up to approximately 3 years). |
| Part B: Median Overall Survival (OS) | 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. | From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months. |
| Part B: Median Time to Second Progression or Death (PFS2) | 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. | From randomisation until analysis cut-off date (up to approximately 3 years). |
| Lake Success |
| New York |
| 11041 |
| United States |
| Research Site | Edegem | 2650 | Belgium |
| Research Site | Liège | 4000 | Belgium |
| Research Site | Wilrijk | 2610 | Belgium |
| Research Site | London | Ontario | N6A 4G5 | Canada |
| Research Site | Greenfield Park | Quebec | J4V 2H1 | Canada |
| Research Site | Montreal | Quebec | H2L 4M1 | Canada |
| Research Site | Brno | 656 53 | Czechia |
| Research Site | Brno | 656 91 | Czechia |
| Research Site | Liberec | 460 63 | Czechia |
| Research Site | Angers | 49933 | France |
| Research Site | Dijon | 21079 | France |
| Research Site | Lyon | 69373 | France |
| Research Site | Lecce | 73100 | Italy |
| Research Site | Mirano | 30035 | Italy |
| Research Site | Naples | 80131 | Italy |
| Research Site | Parma | 43100 | Italy |
| Research Site | Pisa | 56126 | Italy |
| Research Site | Arnhem | 6815 AD | Netherlands |
| Research Site | Maastricht | 6202 AZ | Netherlands |
| Research Site | Nijmegen | 6532 SZ | Netherlands |
| Research Site | Gdansk | 80-214 | Poland |
| Research Site | Warsaw | 02-781 | Poland |
| Research Site | Ivanovo | 153040 | Russia |
| Research Site | Moscow | 115478 | Russia |
| Research Site | Moscow | 125284 | Russia |
| Research Site | Saint Petersburg | 197022 | Russia |
| Research Site | Badalona | 08916 | Spain |
| Research Site | Córdoba | 14004 | Spain |
| Research Site | Girona | 17007 | Spain |
| Research Site | L'Hospitalet de Llobregat | 08908 | Spain |
| Research Site | Madrid | 28050 | Spain |
| Research Site | Palma de Mallorca | 7014 | Spain |
| Research Site | Valencia | 46010 | Spain |
| Research Site | Cardiff | CF14 2TL | United Kingdom |
| Research Site | Exeter | EX2 5DW | United Kingdom |
| Research Site | Manchester | M20 4BX | United Kingdom |
| Research Site | Plymouth | PL6 8DH | United Kingdom |
| Research Site | Torquay | TQ2 7AA | United Kingdom |
| Research Site | Westcliff-on-Sea | SS0 0RY | United Kingdom |
| Derived |
| 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. |
| Redacted CSR synopsis | View source |
| FG001 |
| Part A Cohort 2: Olaparib 300 mg + Abiraterone |
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. |
| FG002 | Part B: Olaparib + Abiraterone | 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. |
| FG003 | Part B: Placebo + Abiraterone | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Part B Double-blind, Randomised Period |
|
|
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.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Part A Cohort 1: Olaparib 200 mg + Abiraterone | 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. |
| BG001 | Part A Cohort 2: Olaparib 300 mg + Abiraterone | 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. |
| BG002 | Part B: Olaparib + Abiraterone | 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. |
| BG003 | Part B: Placebo + Abiraterone | 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. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part A: Percentage of Patients Experiencing Adverse Events (AEs) | 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. | 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. | Posted | Number | Percentage of patients | Cohort 1 and 2: From baseline in Part A (Day 1 for each cohort) up to 30 days following last dose of study treatment. |
|
|
| ||||||||||||||||||||||||||||||||||||
| Primary | Part A: Number of Patients With Dose Limiting Toxicities (DLTs) | 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. | 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. | Posted | Number | Patients | From Day 1 for Cohort 1 and from Day 4 for Cohort 2 up to 14 days treatment with olaparib + abiraterone for 3 patients. |
| ||||||||||||||||||||||||||||||||||||||
| Primary | Part B: Median Radiological Progression-Free Survival (rPFS) Time | 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). | The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. | Posted | Median | 95% Confidence Interval | Months | From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months. |
| |||||||||||||||||||||||||||||||||||||
| Primary | Part B: Percentage of Patients With Progression Events or Death (rPFS) | 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. | The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. | Posted | Number | Percentage of patients | From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months. |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Part A Pharmacokinetics (PK): Olaparib Maximum Plasma Concentration at Steady State (Cmax,ss) | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per millilitre (mcg/mL) | 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. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part A PK: Abiraterone Cmax,ss | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per millilitre (ng/mL) | 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. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part A PK Analysis: Olaparib Time to Reach Maximum Plasma Concentration at Steady State (Tmax,ss) | 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. | 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. | Posted | Median | Full Range | Hours (h) | 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. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part A PK: Abiraterone Tmax,ss | 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. | 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. | Posted | Median | Full Range | Hours | 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. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part A PK Analysis: Olaparib Minimum Plasma Concentration at Steady State (Cmin,ss) | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | 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. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part A PK: Abiraterone Cmin,ss | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part A PK Analysis: Olaparib Area Under the Plasma Concentration-Time Curve at Steady State (AUCss) | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg*h/mL | 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. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part A PK: Abiraterone AUCss | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part B: Percentage of Patients Experiencing AEs | 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. | 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. | Posted | Number | Percentage of patients | 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). |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Part B: Median Best Percentage Change From Baseline in Prostate Specific Antigen (PSA) Levels | 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. | 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. | Posted | Median | Full Range | Percentage change in PSA level | From baseline, then every 4 weeks up to Week 52, and then every 12 weeks. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part B: Percentage of Patients With PSA Responses | 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. | The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. | Posted | Number | 80% Confidence Interval | Percentage of patients | From baseline, then every 4 weeks up to Week 24, and then every 12 weeks. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part B: Median Best Percentage Change From Baseline in Circulating Tumour Cell (CTC) Level | 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. | 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. | Posted | Median | Full Range | Percentage change in CTC level | From baseline, then every 4 weeks up to Week 24, and then every 12 weeks. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part B: Percentage of Patients With at Least One Objective Response (Objective Response Rate [ORR]) | 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. | 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. | Posted | Number | Percentage of patients | From baseline, then every 4 weeks up to Week 52, and then every 12 weeks. |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Median Time to First Subsequent Therapy (TFST) and Median Time to Second Subsequent Therapy (TSST) | 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. | The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. | Posted | Median | 95% Confidence Interval | Months | From randomisation until analysis cut-off date (up to approximately 3 years). |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Part B: Median Overall Survival (OS) | 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. | The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. | Posted | Median | 95% Confidence Interval | Months | From baseline, every 12 weeks up to Week 72, then every 24 weeks up to 24 months. |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Part B: Median Time to Second Progression or Death (PFS2) | 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. | The Full analysis set consisted of all randomised patients in Part B, regardless of treatment actually received. | Posted | Median | 95% Confidence Interval | Months | From randomisation until analysis cut-off date (up to approximately 3 years). |
|
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).
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A Cohort 1: Olaparib 200 mg + Abiraterone | 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. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG001 | Part A Cohort 2: Olaparib 300 mg + Abiraterone | 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. | 1 | 13 | 3 | 13 | 7 | 13 |
| EG002 | Part B: Olaparib + Abiraterone | 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. | 43 | 71 | 25 | 71 | 63 | 71 |
| EG003 | Part B: Placebo + Abiraterone | 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. | 45 | 71 | 14 | 71 | 52 | 71 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cardiac failure chronic | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Eye haemorrhage | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Bacterial infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Mediastinitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pyelonephritis chronic | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Patella fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract stoma complication | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of the tongue | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Thrombotic stroke | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Internal haemorrhage | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Peripheral ischaemia | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cerumen impaction | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tympanic membrane perforation | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Eyelid oedema | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Ocular hyperaemia | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Arthritis infective | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Furuncle | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Wound secretion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood calcium decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Heart rate irregular | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Urine output increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Fluid retention | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Affect lability | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Euphoric mood | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertonic bladder | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Purpura | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Skin atrophy | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | AstraZeneca | +13028851180 | ClinicalTrialTransparency@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 23, 2017 | Sep 6, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C531550 | olaparib |
| C089740 | abiraterone |
| D011241 | Prednisone |
| D011239 | Prednisolone |
| ID | Term |
|---|---|
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D011246 | Pregnadienetriols |
Not provided
Not provided
| Reason not recorded |
|
| Screen failure |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Any AE c-r to abiraterone only |
|
| Any AE CTCAE Grade 3 or higher |
|
| Any AE CTCAE Grade 3 or higher c-r to olaparib |
|
| Any AE CTCAE Grade 3 or higher c-r to abiraterone |
|
| Any AE with outcome = death |
|
| Any serious AE (SAE) |
|
| Any SAE c-r to olaparib |
|
| Any SAE c-r to abiraterone |
|
| Any AE causing discont of olaparib |
|
| Any AE causing discont of olaparib c-r to olaparib |
|
| Any AE causing discont olaparib c-r to abiraterone |
|
| OG001 | Part A Cohort 2: Olaparib 300 mg + Abiraterone | 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. |
|
|
| Part B: Placebo + Abiraterone |
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. |
|
|
| OG001 |
| Part B: Placebo + Abiraterone |
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. |
|
|
|
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. |
|
|
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. |
|
|
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. |
|
|
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.
|
|
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. |
|
|
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.
|
|
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. |
|
|
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.
|
|
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. |
|
|
|
|
|
|
|
|
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. |
|
|
|
|
|
|
| Counts |
|---|
| Participants |
|
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|