Olaparib Maintenance Monotherapy in Patients With BRCA Mu... | NCT01844986

ID	Type	Description	Link
2024-511142-39-00	Registry Identifier	CTIS (EU)
2013-001551-13	EudraCT Number

Name	Class
GOG Foundation	NETWORK
Myriad Genetic Laboratories, Inc.	INDUSTRY
Merck Sharp & Dohme LLC	INDUSTRY

Label	Type	Description	Intervention Names
Olaparib tablets p.o. 300mg twice daily	Experimental	Olaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity	Drug: Olaparib 300mg tablets
Placebo tablets p.o. twice daily	Placebo Comparator	Olaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity	Drug: Olaparib 300mg tablets

Name	Type	Description	Arm Group Labels	Other Names
Olaparib 300mg tablets	Drug	Olaparib/placebo tablets p.o 300mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Measure	Description	Time Frame
Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	To determine the efficacy by progression free survival (PFS) using investigator assessment according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.	Radiologic scans performed at baseline then every 12 weeks up to 156 weeks, then every 24 weeks thereafter until objective radiological disease progression. DCO: 17 May 2018

Measure	Description	Time Frame
Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival	To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of overall survival (OS). Reports results of a pre-specified interim analysis; results for final OS analysis (235 OS events) anticipated 2029.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Female patients with newly diagnosed, histologically confirmed, high risk advanced (FIGO stage III - IV) BRCA mutated high grade serous or high grade endometrioid ovarian cancer, primary peritoneal cancer and / or fallopian - tube cancer who have completed first line platinum based chemotherapy (intravenous or intraperitoneal).
Stage III patients must have had one attempt at optimal debulking surgery (upfront or interval debulking). Stage IV patients must have had either a biopsy and/or upfront or interval debulking surgery.
Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
Patients who have completed first line platinum (e.g. carboplatin or cisplatin), containing therapy (intravenous or intraperitoneal) prior to randomisation:
Patients must have, in the opinion of the investigator, clinical complete response or partial response and have no clinical evidence of disease progression on the post treatment scan or rising CA-125 level, following completion of this chemotherapy course. Patients with stable disease on the post-treatment scan at completion of first line platinum-containing therapy are not eligible for the study.
Patients must be randomized within 8 weeks of their last dose of chemotherapy

Exclusion Criteria:

BRCA1 and/or BRCA2 mutations that are considered to be non detrimental (e.g. "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism" etc).
Patients with early stage disease (FIGO Stage I, IIA, IIB or IIC)
Stable disease or progressive disease on the post-treatment scan or clinical evidence of progression at the end of the patient's first line chemotherapy treatment.
Patients where more than one debulking surgery has been performed before randomisation to the study. (Patients who, at the time of diagnosis, are deemed to be unresectable and undergo only a biopsy or oophorectomy but then go on to receive chemotherapy and interval debulking surgery are eligible).
Patients who have previously been diagnosed and treated for earlier stage ovarian, fallopian tube or primary peritoneal cancer.
Patients who have previously received chemotherapy for any abdominal or pelvic tumour, including treatment for prior diagnosis at an earlier stage for their ovarian, fallopian tube or primary peritoneal cancer. (Patients who have received prior adjuvant chemotherapy for localised breast cancer may be eligible, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease).
Patients with synchronous primary endometrial cancer unless both of the following criteria are met: 1) stage <2 2) less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with Stage IA grade 1 or 2 endometrioid adenocarcinoma. Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.

Name	Affiliation	Role
Prof Paul DiSilvestro, MD	Women & Infants Hospital, Providence, Rhode Island, USA	Principal Investigator
Prof Kathleen Moore, MD	University of Oklahoma Health Sciences Center, Oklahoma City, USA	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Clearview Cancer Institute		Huntsville	Alabama		United States
Providence Cancer Center

PubMed Identifier	Type	Citation	Retractions
39695768	Derived	Barnicle A, Ray-Coquard I, Rouleau E, Cadoo K, Simpkins F, Aghajanian C, Leary A, Poveda A, Lheureux S, Pujade-Lauraine E, You B, Ledermann J, Matulonis U, Gourley C, Timms KM, Lai Z, Hodgson DR, Elks CE, Dearden S, Egile C, Lao-Sirieix P, Harrington EA, Brown JS. Patterns of genomic instability in > 2000 patients with ovarian cancer across six clinical trials evaluating olaparib. Genome Med. 2024 Dec 18;16(1):145. doi: 10.1186/s13073-024-01413-5.
36082969

Label	URL
Redacted Clinical Study Protocol	View source

ID	Title	Description
FG000	Olaparib 300mg Tablets	Taken orally twice daily
FG001	Placebo Tablets	Taken orally twice daily

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 5, 2021	Nov 3, 2022

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

Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

To determine the efficacy by progression free survival (PFS) using investigator assessment according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) [Primary analysis] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Posted

Median

95% Confidence Interval

Months

Radiologic scans performed at baseline then every 12 weeks up to 156 weeks, then every 24 weeks thereafter until objective radiological disease progression. DCO: 17 May 2018

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily
OG002	Olaparib 300mg Tablets (China Cohort)	Taken orally twice daily
OG003	Placebo Tablets (China Cohort)	Taken orally twice daily

Units	Counts
Participants	OG000260 OG001131 OG00244 OG003

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)Insufficient PFS events to estimate median, lower and upper confidence limit. OG00113.8(11.1 to 18.2) OG002NA(NA to NA)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Cox	Model includes a factor for response to previous platinum chemotherapy	<0.0001	Determined using a log-rank test stratified by response to previous platinum chemotherapy	Hazard Ratio (HR)	0.30			2-Sided	95	0.23	0.41			A hazard ratio < 1 favours olaparib		Superiority

Secondary

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of overall survival (OS). Reports results of a pre-specified interim analysis; results for final OS analysis (235 OS events) anticipated 2029.

Posted

Median

95% Confidence Interval

Months

Assessed every 4 weeks until treatment discontinues (up to a max of 156 weeks), then as per protocol. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily
OG002	Olaparib 300mg Tablets (China Cohort)

Secondary

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen-125 (CA-125) or death

Posted

Median

95% Confidence Interval

Months

CA-125 performed at baseline + every 4 weeks. Radiologic scans performed at baseline + every 12 weeks up to 156 weeks, then every 24 weeks until objective radiological disease progression. DCO:17May2018

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily
OG002	Olaparib 300mg Tablets (China Cohort)

Secondary

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression

Posted

Median

95% Confidence Interval

Months

Following first progression disease then assessed per local practice every 12 weeks until second progression.

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily
OG002	Olaparib 300mg Tablets (China Cohort)	Taken orally twice daily

Secondary

Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)

To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) with a baseline and post baseline TOI scores available.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

Questionnaires will be given to the patient at baseline, at Day 29 and then every 12 weeks for 156 weeks, then every 24 weeks or until the data cut off for the PFS analysis, change in TOI over 24 months reported

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily

Secondary

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST)

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to first subsequent therapy or death (TFST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).

Posted

Median

95% Confidence Interval

Months

Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily
OG002

Secondary

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST)

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second subsequent therapy or death (TSST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).

Posted

Median

95% Confidence Interval

Months

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily
OG002

Secondary

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT)

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to study treatment discontinuation or death (TDT). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).

Posted

Median

95% Confidence Interval

Months

Time elapsed from randomization to study treatment discontinuation or death. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily

Secondary

Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS

To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and potential future BRCA mutation assays (gene sequencing and large rearrangement analysis)

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) and confirmed as Myriad gBRCAm.

Posted

Median

95% Confidence Interval

Months

Radiologic scans performed at baseline then every 12 weeks for the first 156 weeks, then every 24 weeks thereafter, assessed until disease progression. Analysis of data assessed up to a maximum of 54 months.

ID	Title	Description
OG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily
OG001	Placebo Tablets (Global Cohort)	Taken orally twice daily

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00036 events17 affected260 at risk EG0010 events0 affected130 at risk EG00210 events8 affected44 at risk EG0030 events0 affected20 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0010 events0 affected130 at risk EG0022 events2 affected44 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Incarcerated umbilical hernia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Chills	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Incarcerated hernia	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Cystitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Infected lymphocele	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Lung infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Medical device site cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 events3 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Wound infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0012 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Platelet count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0011 events1 affected130 at risk EG0021 events1 affected44 at risk EG003
Cell death	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Lip and/or oral cavity cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Splenic cyst	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Subileus	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Appendicitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Urosepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Viral infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Accidental exposure to product by child	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Drug administration error	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Stab wound	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Wound complication	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Abdominal wall neoplasm benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0021 events1 affected44 at risk EG003
Breast cancer female	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0013 events3 affected130 at risk EG0020 events0 affected44 at risk EG003
Intraductal proliferative breast lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Thyroid cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Ataxia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0012 events2 affected130 at risk EG0020 events0 affected44 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Syncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Depression	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 events2 affected260 at risk EG0010 events0 affected130 at risk EG0020 events0 affected44 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG000156 events90 affected260 at risk EG00118 events12 affected130 at risk EG00244 events21 affected44 at risk EG0033 events3 affected20 at risk
Palpitations	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG00019 events12 affected260 at risk EG0012 events2 affected130 at risk EG0026 events3 affected44 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00010 events8 affected260 at risk EG0013 events2 affected130 at risk EG0028 events5 affected44 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00022 events18 affected260 at risk EG00110 events10 affected130 at risk EG0023 events2 affected44 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00086 events63 affected260 at risk EG00128 events25 affected130 at risk EG0024 events2 affected44 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0008 events8 affected260 at risk EG0014 events4 affected130 at risk EG0022 events1 affected44 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00050 events43 affected260 at risk EG00118 events16 affected130 at risk EG0022 events2 affected44 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG000412 events201 affected260 at risk EG00175 events49 affected130 at risk EG00249 events28 affected44 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00037 events23 affected260 at risk EG0015 events3 affected130 at risk EG0020 events0 affected44 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0008 events8 affected260 at risk EG0014 events4 affected130 at risk EG0023 events3 affected44 at risk EG003
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG000138 events106 affected260 at risk EG00148 events39 affected130 at risk EG00222 events16 affected44 at risk EG003
Influenza like illness	General disorders	MedDRA 21.0	Systematic Assessment	EG00029 events19 affected260 at risk EG00111 events11 affected130 at risk EG0020 events0 affected44 at risk EG003
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG00032 events24 affected260 at risk EG00110 events9 affected130 at risk EG0020 events0 affected44 at risk EG003
Cystitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00019 events15 affected260 at risk EG0018 events5 affected130 at risk EG0020 events0 affected44 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00036 events28 affected260 at risk EG00115 events12 affected130 at risk EG00220 events17 affected44 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00013 events9 affected260 at risk EG0018 events8 affected130 at risk EG00223 events6 affected44 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00013 events11 affected260 at risk EG0017 events6 affected130 at risk EG00215 events6 affected44 at risk EG003
Blood creatinine increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00030 events21 affected260 at risk EG0014 events2 affected130 at risk EG0023 events2 affected44 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00017 events13 affected260 at risk EG00115 events10 affected130 at risk EG0020 events0 affected44 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00088 events66 affected260 at risk EG00147 events35 affected130 at risk EG0022 events2 affected44 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00050 events40 affected260 at risk EG00122 events16 affected130 at risk EG0026 events3 affected44 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00036 events28 affected260 at risk EG00117 events13 affected130 at risk EG0022 events2 affected44 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00034 events28 affected260 at risk EG00115 events11 affected130 at risk EG0024 events1 affected44 at risk EG003
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0010 events0 affected130 at risk EG0024 events3 affected44 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00033 events16 affected260 at risk EG0015 events5 affected130 at risk EG00264 events15 affected44 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00084 events40 affected260 at risk EG00111 events9 affected130 at risk EG00268 events17 affected44 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00052 events21 affected260 at risk EG0014 events2 affected130 at risk EG00235 events13 affected44 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00061 events46 affected260 at risk EG00122 events17 affected130 at risk EG00214 events9 affected44 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00097 events72 affected260 at risk EG00130 events25 affected130 at risk EG00210 events8 affected44 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG000205 events89 affected260 at risk EG00158 events32 affected130 at risk EG00212 events8 affected44 at risk EG003
Gastric dilatation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected260 at risk EG0011 events1 affected130 at risk EG0021 events1 affected44 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00011 events5 affected260 at risk EG0010 events0 affected130 at risk EG0026 events5 affected44 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG000242 events104 affected260 at risk EG00126 events19 affected130 at risk EG00238 events18 affected44 at risk EG003
Asthenia	General disorders	MedDRA 21.0	Systematic Assessment	EG000131 events63 affected260 at risk EG00120 events16 affected130 at risk EG0026 events3 affected44 at risk EG003
Mucosal inflammation	General disorders	MedDRA 21.0	Systematic Assessment	EG00027 events17 affected260 at risk EG0011 events1 affected130 at risk EG0020 events0 affected44 at risk EG003
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG00040 events31 affected260 at risk EG00115 events12 affected130 at risk EG0028 events8 affected44 at risk EG003
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00024 events19 affected260 at risk EG0013 events3 affected130 at risk EG0020 events0 affected44 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00038 events27 affected260 at risk EG00137 events17 affected130 at risk EG00216 events5 affected44 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00011 events9 affected260 at risk EG0016 events3 affected130 at risk EG0025 events4 affected44 at risk EG003
Sinusitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00012 events11 affected260 at risk EG0018 events8 affected130 at risk EG0020 events0 affected44 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00052 events29 affected260 at risk EG00110 events8 affected130 at risk EG0024 events4 affected44 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00040 events20 affected260 at risk EG00114 events7 affected130 at risk EG00217 events7 affected44 at risk EG003
Platelet count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00012 events8 affected260 at risk EG0014 events2 affected130 at risk EG00219 events6 affected44 at risk EG003
Weight increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00015 events13 affected260 at risk EG00112 events12 affected130 at risk EG0020 events0 affected44 at risk EG003
White blood cell count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00037 events16 affected260 at risk EG0019 events6 affected130 at risk EG00228 events10 affected44 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00068 events51 affected260 at risk EG00119 events13 affected130 at risk EG00222 events17 affected44 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00024 events15 affected260 at risk EG0016 events3 affected130 at risk EG00210 events3 affected44 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00022 events17 affected260 at risk EG0011 events1 affected130 at risk EG0021 events1 affected44 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00017 events16 affected260 at risk EG00113 events11 affected130 at risk EG0021 events1 affected44 at risk EG003
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00068 events51 affected260 at risk EG00123 events20 affected130 at risk EG00210 events8 affected44 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00092 events68 affected260 at risk EG0016 events5 affected130 at risk EG0024 events3 affected44 at risk EG003
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG000109 events58 affected260 at risk EG00140 events30 affected130 at risk EG0029 events7 affected44 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0006 events5 affected260 at risk EG0013 events2 affected130 at risk EG0024 events4 affected44 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00015 events15 affected260 at risk EG0019 events7 affected130 at risk EG0020 events0 affected44 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG00015 events15 affected260 at risk EG00111 events11 affected130 at risk EG0021 events1 affected44 at risk EG003
Depression	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG00014 events12 affected260 at risk EG00115 events13 affected130 at risk EG0022 events2 affected44 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG00031 events27 affected260 at risk EG00120 events16 affected130 at risk EG0023 events3 affected44 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00057 events42 affected260 at risk EG00137 events28 affected130 at risk EG0026 events5 affected44 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00053 events39 affected260 at risk EG0017 events7 affected130 at risk EG0020 events0 affected44 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00026 events21 affected260 at risk EG00115 events12 affected130 at risk EG0023 events3 affected44 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00023 events16 affected260 at risk EG00111 events11 affected130 at risk EG0024 events2 affected44 at risk EG003
Hot flush	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG00025 events17 affected260 at risk EG00112 events11 affected130 at risk EG0021 events1 affected44 at risk EG003
Hypertension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG00018 events9 affected260 at risk EG00117 events12 affected130 at risk EG0021 events1 affected44 at risk EG003

ID	Title	Description
BG000	Olaparib 300mg Tablets (Global Cohort & China Cohort)	Taken orally twice daily
BG001	Placebo Tablets (Global Cohort & China Cohort)	Taken orally twice daily
BG002	Total	Total of all reporting groups

ID	Term
D000095384	Pathologic Complete Response
D010051	Ovarian Neoplasms

ID	Term
D018450	Disease Progression
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D000091662	Genital Diseases
D004700	Endocrine System Diseases
D006058	Gonadal Disorders

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Olaparib 300mg Tablets (Global Cohort)	Taken orally twice daily	55	260	54	260	253	260
EG001	Placebo Tablets (Global Cohort)	Taken orally twice daily	27	131	16	130	117	130
EG002	Olaparib 300mg Tablets (China Cohort)	Taken orally twice daily	10	44	13	44	43	44
EG003	Placebo Tablets (China Cohort)	Taken orally twice daily	6	20	3	20	18	20