To Determine the effect of Food on the Pharmacokinetics of Olaparib and the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients with Advanced Solid Tumours

Study identifier:D0816C00004

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Randomised, Open-label, Three-part, Phase I Study to Determine the Effect of Food on the Pharmacokinetics of Olaparib and to Provide Data on the Effect of Olaparib on QT Interval Following Oral Dosing of a Tablet Formulation in Patients with Advanced Solid Tumours

Medical condition

Solid tumours

Phase

Phase 1

Healthy volunteers

Study drug

Olaparib tablets

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 24 Sept 2013

Primary Completion Date: 08 Apr 2014

Study Completion Date: 15 Mar 2022

Study design

Allocation: Randomized
Endpoint Classification: Pharmacokinetics/dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Other

Verification:

Verified 01 Dec 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

-
For inclusion in the study, patients should fulfil the following criteria:
1. Provision of written informed consent prior to any study specific procedures.
2. Patients aged greater than or equal to 18 years.
3. Able to eat a high-fat meal within a 30-minute period, as provided by the study site.
4. Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
5. Normal organ and bone marrow function measured within 28 days prior to administration of investigational product (IP) as defined below:
Haemoglobin greater than or equal to 10.0 g/dL, with no blood transfusions in the previous 28 days.
Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L.
White blood cells (WBC) greater than 3 x 109/L.
Platelet count greater than or equal to 100 x 109/L.
Total bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN) except in the case of Gilbert's disease.
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) less than or equal to 2.5 x institutional ULN unless liver metastases are present in which case it must be less than or equal to 5 x ULN.
Serum creatinine less than or equal to 1.5 x institutional ULN.
Serum potassium, sodium, magnesium and calcium within the institutional normal range.
6. Calculated serum creatinine clearance greater than 50 mL/min (using Cockroft-Gault formula or by 24-hour urine collection).
7. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. 8. Patients must have a life expectancy of greater than or equal to 16 weeks.
9. Evidence of non-childbearing status for women of childbearing potential, or post-menopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on Day 1 of the first treatment period in Part A. Postmenopausal is defined as:
Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments. Luteinising hormone and follicle stimulating hormone levels in the post-menopausal range for women under 50 years of age.
Radiation-induced oophorectomy with last menses greater than 1 year ago.
Chemotherapy-induced menopause with greater than 1 year interval since last menses.
Surgical sterilisation (bilateral oophorectomy or hysterectomy).
10. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
11. Patients must be on a stable concomitant medication regimen (with the exception of electrolyte supplements), defined as no changes in medication or in dose within 2 weeks prior to start of olaparib dosing, except for bisphosphonates, denosumab, and corticosteroids, which should be stable for at least 4 weeks prior to start of olaparib dosing.

Exclusion Criteria

-
1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff, its agents, and/or staff at the study site).
2. Previous enrolment in the present study.
3. Participation in another clinical study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases before and during the study as long as these were started at least 4 weeks prior to treatment.
5. Patients who have received or are receiving inhibitors or inducers of CYP3A4.
6. Toxicities (greater than or equal to CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia.
7. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patients with asymptomatic brain metastases or with symptomatic but stable brain metastases can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment.
8. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
9. Patients unable to fast for up to 14 hours.
10. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, uncontrolled seizures, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive bilateral interstitial lung disease on high resolution computed tomography (HRCT) scan, or any psychiatric disorder that prohibits obtaining informed consent.
11. Patients with a history of poorly controlled hypertension with resting blood pressure (BP) greater than 150/100 mm Hg in the presence or absence of a stable regimen of hypertensive therapy. Measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2 minute intervals and averaged. If the first 2 diastolic readings differ by more than 5 mm Hg, an additional reading should be obtained and averaged.
12. Patients with a history of heart failure or left ventricular dysfunction, and patients who require calcium channel blockers.
13. Patients with type I or type II diabetes.
14. Patients who have gastric, gastro-oesophageal or oesophageal cancer.
15. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with absorption of olaparib.
16. Breastfeeding women.
17. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
18. Patients with known active hepatic disease (ie, hepatitis B or C).
19. Patients with a known hypersensitivity to olaparib or any of the excipients of the product. 20. Mean QTc with Fridericia's correction (QTcF) greater than 470 ms in screening ECG or history of familial long QT syndrome:
A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval greater than 470 ms).
A history of additional risk factors for Torsade de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).
21. The use of concomitant medications that prolong the QT/QTc interval.
22. Clinical judgment by the investigator that the patient should not participate in the study

Location

Research Site

Brussels, Belgium, 1090

Location

Research Site

Leuven, Belgium, 3000

Location

Research Site

Liege, Belgium, 4000

Location

Research Site

Herlev, Denmark, 2730

Location

Research Site

København Ø, Denmark, 2100

Location

Research Site

Maastricht, Netherlands, 6202 AZ

Location

Research Site

Nijmegen, Netherlands, 6525 GA

Location

Research Site

UTRECHT, Netherlands, 3584 CX

Arms	Assigned Interventions
Other: Fasted Olaparib tablets following no breakfast	Drug: Olaparib tablets Olaparib dosing (2X 150mg tablets) following allocated meal Procedure/Surgery: Pharmacokinetic sampling Blood samples taken pre and post dosing with 2x 150 mg olaparib tablet Other: Dietary Fasted 2x 150 mg olaparib tablet formulation taken in fasted state. 5-14 days washout period
Other: High-fat meal Olaparib tablets after high-fat breakfast	Drug: Olaparib tablets Olaparib dosing (2X 150mg tablets) following allocated meal Procedure/Surgery: Pharmacokinetic sampling Blood samples taken pre and post dosing with 2x 150 mg olaparib tablet Other: Dietary High Fat 2x 150 mg olaparib tablet formulation taken 30 minutes after allocated meal. 5-14 days washout period.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This Phase 1, 3-part (Part A, B and C) study was conducted in participants with advanced solid tumours at 11 sites in 4 countries (Belgium, Denmark, The Netherlands, and United Kingdom). First participant was enrolled on 24-Sep-2013 and data cut-off (DCO) for Parts A and B was 12-May-2014 and DCO for Part C was 03-Sep-2015.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Study consists of a screening period (28 days), treatment period (Part A: open-label, 2-treatment period crossover study; Part B: open-label study; and Part C: continued access study) and follow-up period (up to 30 days). A total of 60 participants were enrolled in the study.

Reporting Groups

	Description
Part A: Olaparib - Fed then Fasted	Participants received a single olaparib 300 milligram (mg) tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in period 1 and overnight fasted in period 2.
Part A: Olaparib - Fasted then Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in period 1 and fed with high fat meal at breakfast time in period 2.
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.
Part C: Olaparib	Eligible participants continued to receive olaparib 300 mg tablets orally twice daily for 12 months.

Participant Flow for 3 periods

Period 1: Part A

	Part A: Olaparib - Fed then Fasted	Part A: Olaparib - Fasted then Fed
STARTED	32	28
COMPLETED	32	28
NOT COMPLETED	0	0

Period 2: Part B

	Part A: Olaparib - Fed then Fasted	Part A: Olaparib - Fasted then Fed	Part B: Olaparib	Part C: Olaparib
STARTED	0	0	60	0
Received Treatment in Part B	0	0	57	0
COMPLETED	0	0	56	0
NOT COMPLETED	0	0	4	0
Condition under investigation worsened	0	0	1	0
Did not continued into Part B	0	0	3	0

Period 3: Part C

	Part A: Olaparib - Fed then Fasted	Part A: Olaparib - Fasted then Fed	Part B: Olaparib	Part C: Olaparib
STARTED	0	0	0	55
COMPLETED	0	0	0	4
NOT COMPLETED	0	0	0	51
Subject Decision	0	0	0	1
Lack of therapeutic response	0	0	0	4
Death	0	0	0	1
Condition under investigation worsened	0	0	0	41
Adverse Event	0	0	0	4

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The safety analysis set included all participants who received at least 1 dose of olaparib.

Reporting Groups

	Description
Part A: Olaparib - Fed then Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in period 1 and overnight fasted in period 2.
Part A: Olaparib - Fasted then Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in period 1 and fed with high fat meal at breakfast time in period 2.

Baseline Measures

	Part A: Olaparib - Fed then Fasted	Part A: Olaparib - Fasted then Fed	Total
Number of Participants [units: Participants]	32	28	60
Age Continuous [units: years] Mean ± Standard Deviation	60.5 ± 12.86	58.0 ± 10.16	59.3 ± 11.65
Age, Customized [units: participants]
<40	2	1	3
>=40 - <65	17	19	36
>=65	13	8	21
Sex: Female, Male [units: participants]
Female	25	21	46
Male	7	7	14
Race/Ethnicity, Customized [units: participants]
White	32	27	59
Black or African American	0	0	0
Asian	0	0	0
Native Hawaiian or other Pacific Islander	0	0	0
American Indian or Alaska Native	0	0	0
Other	0	1	1
Race/Ethnicity, Customized [units: participants]
Hispanic or Latino	0	0	0
Not Hispanic or Latino	32	28	60

Outcome Measures

1. Primary Outcome Measure: Part A: Maximum Plasma Concentration (Cmax) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Maximum Plasma Concentration (Cmax) of Olaparib
Measure Description	Cmax was obtained directly from the observed concentration versus time data. Cmax calculated using log transformed data.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	54	55
Part A: Maximum Plasma Concentration (Cmax) of Olaparib [units: microgram/milliliter (mcg/mL)] Geometric Mean (Geometric Coefficient of Variation)	5.476 (40.5%)	7.004 (35.0%)

No statistical analysis provided for Part A: Maximum Plasma Concentration (Cmax) of Olaparib

2. Primary Outcome Measure: Part A: Time to Reach Maximum Plasma Concentration (tmax) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Time to Reach Maximum Plasma Concentration (tmax) of Olaparib
Measure Description	Tmax was obtained directly from the observed concentration versus time data.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	54	55
Part A: Time to Reach Maximum Plasma Concentration (tmax) of Olaparib [units: hour] Median (Full Range)	4.00 (1.00 to 11.97)	1.50 (0.50 to 5.85)

No statistical analysis provided for Part A: Time to Reach Maximum Plasma Concentration (tmax) of Olaparib

3. Primary Outcome Measure: Part A: Area Under the Plasma Concentration Time Curve From Zero to 12 Hours (AUC0-12) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Area Under the Plasma Concentration Time Curve From Zero to 12 Hours (AUC0-12) of Olaparib
Measure Description	AUC0-12 was calculated by linear up/log down trapezoidal summation. The AUC0-12 calculated using log transformed data.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	54	55
Part A: Area Under the Plasma Concentration Time Curve From Zero to 12 Hours (AUC0-12) of Olaparib [units: mcg*hour (h)/mL] Geometric Mean (Geometric Coefficient of Variation)	32.59 (45.8%)	35.44 (45.7%)

No statistical analysis provided for Part A: Area Under the Plasma Concentration Time Curve From Zero to 12 Hours (AUC0-12) of Olaparib

4. Primary Outcome Measure: Part A: Area Under the Plasma Concentration Time Curve From Zero to the Last Measurable Time Point (AUC0-t) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Area Under the Plasma Concentration Time Curve From Zero to the Last Measurable Time Point (AUC0-t) of Olaparib
Measure Description	AUC0-t was calculated by linear up/log down trapezoidal summation. The AUC0-t calculated using log transformed data.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	51	52
Part A: Area Under the Plasma Concentration Time Curve From Zero to the Last Measurable Time Point (AUC0-t) of Olaparib [units: mcg*h/mL] Geometric Mean (Geometric Coefficient of Variation)	46.03 (56.6%)	43.60 (54.3%)

No statistical analysis provided for Part A: Area Under the Plasma Concentration Time Curve From Zero to the Last Measurable Time Point (AUC0-t) of Olaparib

5. Primary Outcome Measure: Part A: Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC0-inf) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC0-inf) of Olaparib
Measure Description	AUC0-inf was calculated by linear up/log down trapezoidal summation and extrapolated to infinity by the addition of the last quantifiable concentration divided by the terminal rate constant (AUC0-t+Clast/lambda_z). The AUC0-inf calculated using log transformed data.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	51	54
Part A: Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC0-inf) of Olaparib [units: mcg*h/mL] Geometric Mean (Geometric Coefficient of Variation)	45.42 (57.1%)	42.98 (55.2%)

No statistical analysis provided for Part A: Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC0-inf) of Olaparib

6. Primary Outcome Measure: Part A: Apparent Plasma Clearance (CL/F) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Apparent Plasma Clearance (CL/F) of Olaparib
Measure Description	CL/F for olaparib was estimated as dose divided by AUC.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	51	54
Part A: Apparent Plasma Clearance (CL/F) of Olaparib [units: Liters/hour (L/h)] Mean (Standard Deviation)	7.548 (3.989)	7.947 (4.226)

No statistical analysis provided for Part A: Apparent Plasma Clearance (CL/F) of Olaparib

7. Primary Outcome Measure: Part A: Apparent Volume of Distribution (Vz/F) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Apparent Volume of Distribution (Vz/F) of Olaparib
Measure Description	Vz/F was estimated as CL/F divided by lambda_z.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	51	54
Part A: Apparent Volume of Distribution (Vz/F) of Olaparib [units: Liter] Mean (Standard Deviation)	127.3 (106.9)	146.2 (142.1)

No statistical analysis provided for Part A: Apparent Volume of Distribution (Vz/F) of Olaparib

8. Primary Outcome Measure: Part A: Terminal Rate Constant (lambda_z) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Terminal Rate Constant (lambda_z) of Olaparib
Measure Description	Lambda_z was estimated by log-linear least squares regression of the terminal part of the concentration-time curve. Lambda_z calculated using log transformed data.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	51	54
Part A: Terminal Rate Constant (lambda_z) of Olaparib [units: per hour] Geometric Mean (Geometric Coefficient of Variation)	0.067494 (47.5%)	0.061718 (42.7%)

No statistical analysis provided for Part A: Terminal Rate Constant (lambda_z) of Olaparib

9. Primary Outcome Measure: Part A: Terminal Half-Life (t½) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1 ]

Measure Type	Primary
Measure Name	Part A: Terminal Half-Life (t½) of Olaparib
Measure Description	T1/2 was calculated using visual assessment to identify the terminal linear phase of the concentration-time profile.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part A) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	51	54
Part A: Terminal Half-Life (t½) of Olaparib [units: hour] Mean (Standard Deviation)	11.14 (4.090)	12.20 (5.307)

No statistical analysis provided for Part A: Terminal Half-Life (t½) of Olaparib

10. Primary Outcome Measure: Part B: Maximum Plasma Concentration of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Maximum Plasma Concentration of Olaparib
Measure Description	Cmax was obtained directly from the observed concentration versus time data. Cmax calculated using log transformed data.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Maximum Plasma Concentration of Olaparib [units: mcg/mL] Geometric Mean (Geometric Coefficient of Variation)	9.173 (34.3%)

No statistical analysis provided for Part B: Maximum Plasma Concentration of Olaparib

11. Primary Outcome Measure: Part B: Minimum Plasma Concentration (Cmin) of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Minimum Plasma Concentration (Cmin) of Olaparib
Measure Description	Cmin was obtained directly from the observed concentration versus time data. Cmin calculated using log transformed data.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Minimum Plasma Concentration (Cmin) of Olaparib [units: mcg/mL] Geometric Mean (Geometric Coefficient of Variation)	1.759 (97.7%)

No statistical analysis provided for Part B: Minimum Plasma Concentration (Cmin) of Olaparib

12. Primary Outcome Measure: Part B: Time to Reach Maximum Plasma Concentration of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Time to Reach Maximum Plasma Concentration of Olaparib
Measure Description	Tmax was obtained directly from the observed concentration versus time data.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Time to Reach Maximum Plasma Concentration of Olaparib [units: hour] Median (Full Range)	1.50 (0.50 to 6.03)

No statistical analysis provided for Part B: Time to Reach Maximum Plasma Concentration of Olaparib

13. Primary Outcome Measure: Part B: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval tau (AUC 0-tau) of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval tau (AUC 0-tau) of Olaparib
Measure Description	AUC 0-tau was calculated by linear up/ log down trapezoidal summation. AUC0-tau calculated using log transformed data.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval tau (AUC 0-tau) of Olaparib [units: mcg*h/mL] Geometric Mean (Geometric Coefficient of Variation)	58.32 (44.5%)

No statistical analysis provided for Part B: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval tau (AUC 0-tau) of Olaparib

14. Primary Outcome Measure: Part B: Apparent Plasma Clearance of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Apparent Plasma Clearance of Olaparib
Measure Description	CL/F for olaparib was estimated as dose divided by AUC.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Apparent Plasma Clearance of Olaparib [units: L/h] Mean (Standard Deviation)	5.605 (2.345)

No statistical analysis provided for Part B: Apparent Plasma Clearance of Olaparib

15. Primary Outcome Measure: Part B: Fluctuation Index (FI) of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Fluctuation Index (FI) of Olaparib
Measure Description	Fluctuation index (%) was calculated = (maximum plasma drug concentration at steady state [Css,max] minus minimum plasma concentration at steady state [Css,min]/ average plasma drug concentration over the dosing interval at steady state [Css,avg]) multiplied by 100. The FI calculated using log transformed data.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Fluctuation Index (FI) of Olaparib [units: percentage fluctuation] Geometric Mean (Geometric Coefficient of Variation)	141.1 (45.9%)

No statistical analysis provided for Part B: Fluctuation Index (FI) of Olaparib

16. Primary Outcome Measure: Part B: Temporal Change Parameter (TCP) of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Temporal Change Parameter (TCP) of Olaparib
Measure Description	TCP is the ratio of AUCtau/ AUC. The TCP calculated using log transformed data.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	47
Part B: Temporal Change Parameter (TCP) of Olaparib [units: ratio] Geometric Mean (Geometric Coefficient of Variation)	1.454 (32.1%)

No statistical analysis provided for Part B: Temporal Change Parameter (TCP) of Olaparib

17. Primary Outcome Measure: Part B: Accumulation Ratio Based on Multiple Dose AUC tau/Single Dose AUC (0-12) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 1 of Part A; Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 of Part B ]

Measure Type	Primary
Measure Name	Part B: Accumulation Ratio Based on Multiple Dose AUC tau/Single Dose AUC (0-12) of Olaparib
Measure Description	Rac (AUC) accumulation ratio was based on multiple dose AUCtau / single dose AUC(0-12). The Rac(AUC) calculated using log transformed data.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 1 of Part A; Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 of Part B
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	48
Part B: Accumulation Ratio Based on Multiple Dose AUC tau/Single Dose AUC (0-12) of Olaparib [units: ratio] Geometric Mean (Geometric Coefficient of Variation)	1.723 (29.7%)

No statistical analysis provided for Part B: Accumulation Ratio Based on Multiple Dose AUC tau/Single Dose AUC (0-12) of Olaparib

18. Primary Outcome Measure: Part B: Accumulation Ratio Based on Cmax Ratio of Multiple Dose to Single Dose (Rac [Cmax]) of Olaparib [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 1 of Part A; Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 of Part B ]

Measure Type	Primary
Measure Name	Part B: Accumulation Ratio Based on Cmax Ratio of Multiple Dose to Single Dose (Rac [Cmax]) of Olaparib
Measure Description	Rac (Cmax) accumulation ratio was based on Cmax ratio of multiple dose to single dose. The Rac(Cmax) calculated using log transformed data.
Time Frame	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 1 of Part A; Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 of Part B
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Accumulation Ratio Based on Cmax Ratio of Multiple Dose to Single Dose (Rac [Cmax]) of Olaparib [units: ratio] Geometric Mean (Geometric Coefficient of Variation)	1.358 (25.1%)

No statistical analysis provided for Part B: Accumulation Ratio Based on Cmax Ratio of Multiple Dose to Single Dose (Rac [Cmax]) of Olaparib

19. Primary Outcome Measure: Part B: Average Plasma Drug Concentration Over the Dosing Interval (Cavg) of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Average Plasma Drug Concentration Over the Dosing Interval (Cavg) of Olaparib
Measure Description	Cavg was calculated as AUC0-tau/tau. Cavg calculated using log transformed data.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Average Plasma Drug Concentration Over the Dosing Interval (Cavg) of Olaparib [units: mcg/mL] Geometric Mean (Geometric Coefficient of Variation)	4.860 (44.5%)

No statistical analysis provided for Part B: Average Plasma Drug Concentration Over the Dosing Interval (Cavg) of Olaparib

20. Primary Outcome Measure: Part B: Time to Reach Minimum Plasma Concentration (tmin) of Olaparib [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5 ]

Measure Type	Primary
Measure Name	Part B: Time to Reach Minimum Plasma Concentration (tmin) of Olaparib
Measure Description	Tmin was obtained directly from the observed concentration versus time data.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours postdose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set (Part B) included all participants who received an olaparib dose and provided evaluable PK profiles in at least 1 treatment period. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	49
Part B: Time to Reach Minimum Plasma Concentration (tmin) of Olaparib [units: hour] Median (Full Range)	12.00 (0.00 to 12.0)

No statistical analysis provided for Part B: Time to Reach Minimum Plasma Concentration (tmin) of Olaparib

21. Secondary Outcome Measure: Part A: Change From Baseline in Corrected QT (QTc) Interval Through 24 Hours Post-dose on Day 1 [ Time Frame: Baseline (Pre-dose) and 0.5, 1, 1.5, 2, 3, 4 ,6 ,8 ,12, and 24 hours post-dose on Day 1 ]

Measure Type	Secondary
Measure Name	Part A: Change From Baseline in Corrected QT (QTc) Interval Through 24 Hours Post-dose on Day 1
Measure Description	The QT interval was corrected for RR (the duration of a heart beat) to obtain corrected (QTc) variables like corrected QT interval for heart rate using Fridericia’s correction (QTcF), corrected QT interval for heart rate using Bazett’s correction (QTcB), and corrected QT interval for heart rate using Individual correction (QTcI). The general formula for QTc was QTc=QT/RR. Baseline (pre-dose) was defined as the pre-dose measurement taken on the same day that the post-dose measurements were taken.
Time Frame	Baseline (Pre-dose) and 0.5, 1, 1.5, 2, 3, 4 ,6 ,8 ,12, and 24 hours post-dose on Day 1
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The QT analysis set included all participants who had at least 1 evaluable time-matched QT/QTc interval value at a scheduled time point, time-matched between Day -1 (baseline) and Day 1 (treatment periods 1 or 2) for Part A. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.

Measured Values

	Part A: Olaparib - Fed	Part A: Olaparib - Fasted
Number of Participants Analyzed [units:participants]	56	59
Part A: Change From Baseline in Corrected QT (QTc) Interval Through 24 Hours Post-dose on Day 1 [units: millisecond (msec)] Mean (Standard Deviation)
QTcF, 0.5 hour post dose	0.8 (10.38)	3.1 (11.03)
QTcF, 1 hour post dose	-0.3 (7.80)	5.8 (9.70)
QTcF, 1.5 hour post dose	-2.9 (7.86)	7.3 (9.84)
QTcF, 2 hour post dose	0.6 (9.73)	6.7 (10.63)
QTcF, 3 hour post dose	-1.2 (9.66)	5.9 (9.89)
QTcF, 4 hour post dose	-0.8 (9.30)	5.3 (13.37)
QTcF, 6 hour post dose	-2.0 (10.60)	-0.8 (14.62)
QTcF, 8 hour post dose	-2.0 (11.14)	-2.6 (12.77)
QTcF, 12 hour post dose	-3.5 (10.09)	0.7 (11.98)
QTcF, 24 hour post dose	-4.9 (11.97)	-3.5 (13.67)

No statistical analysis provided for Part A: Change From Baseline in Corrected QT (QTc) Interval Through 24 Hours Post-dose on Day 1

22. Secondary Outcome Measure: Part B: Change From Baseline in Corrected QT (QTc) Interval Through 12 Hours Post-dose on Day 1 [ Time Frame: Baseline (Pre-dose) and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 5 ]

Measure Type	Secondary
Measure Name	Part B: Change From Baseline in Corrected QT (QTc) Interval Through 12 Hours Post-dose on Day 1
Measure Description	The QT interval was corrected for RR (the duration of a heart beat) to obtain QTc variables like corrected QT interval for heart rate using QTcF, corrected QT interval for heart rate using QTcB, and corrected QT interval for heart rate using QTcI. The general formula for QTc was QTc=QT/RR. Baseline (pre-dose) was defined as the pre-dose measurement taken on the same day that the post-dose measurements were taken.
Time Frame	Baseline (Pre-dose) and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 5
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The QT analysis set included all participants who had at least 1 evaluable time-matched QT/QTc interval value at a scheduled time point, time-matched between Day -1 (baseline) and Day 5 for Part B. Only data from the participants analyzed were reported.

Reporting Groups

	Description
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.

Measured Values

	Part B: Olaparib
Number of Participants Analyzed [units:participants]	54
Part B: Change From Baseline in Corrected QT (QTc) Interval Through 12 Hours Post-dose on Day 1 [units: msec] Mean (Standard Deviation)
QTcF, 1 hour post dose	2.0 (8.06)
QTcF, 1.5 hour post dose	4.1 (8.83)
QTcF, 2 hour post dose	3.6 (9.89)
QTcF, 3 hour post dose	4.1 (10.88)
QTcF, 4 hour post dose	3.9 (10.10)
QTcF, 6 hour post dose	-4.0 (8.73)
QTcF, 8 hour post dose	-6.6 (11.09)
QTcF, 12 hour post dose	-6.0 (13.26)

No statistical analysis provided for Part B: Change From Baseline in Corrected QT (QTc) Interval Through 12 Hours Post-dose on Day 1

Serious Adverse Events

Time Frame	Part A and B: Treatment-emergent adverse events (TEAEs) were reported from first dose of olaparib (Day 1) for that part/treatment period up to first dose of the next part/treatment period. Part C: TEAEs were reported from first dose of olaparib in Part C up to 30 days after the last dose in Part C. Approximately maximum of 15 months.
Additional Description	The safety analysis set included all participants who received at least 1 dose of olaparib. MedDRA version 17 used to report AEs for Part A and B.

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.
Part C: Olaparib	Eligible participants continued to receive olaparib 300 mg tablets orally twice daily for 12 months.

Serious Adverse Events

Part A: Olaparib - Fed

Part A: Olaparib - Fasted

Part B: Olaparib

Part C: Olaparib

Total, serious adverse events

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

0/60 (0.00%)

10/60 (16.67%)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

MALIGNANT PLEURAL EFFUSION¹,^†

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

0/60 (0.00%)

# events

PSYCHIATRIC DISORDERS

PSYCHOTIC DISORDER¹,^†

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

PNEUMONITIS¹,^†

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

# events

BLOOD AND LYMPHATIC SYSTEM DISORDERS

ANAEMIA¹,^†

# participants affected / at risk

0/60 (0.00%)

3/60 (5.00%)

# events

GASTROINTESTINAL DISORDERS

VOMITING¹,^†

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

PYREXIA¹,^†

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

# events

INFECTIONS AND INFESTATIONS

LOWER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

# events

INFECTIONS AND INFESTATIONS

PNEUMONIA¹,^†

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

BACK PAIN¹,^†

# participants affected / at risk

0/60 (0.00%)

1/60 (1.67%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 17.1

Other Adverse Events

Time Frame	Part A and B: Treatment-emergent adverse events (TEAEs) were reported from first dose of olaparib (Day 1) for that part/treatment period up to first dose of the next part/treatment period. Part C: TEAEs were reported from first dose of olaparib in Part C up to 30 days after the last dose in Part C. Approximately maximum of 15 months.
Additional Description	The safety analysis set included all participants who received at least 1 dose of olaparib. MedDRA version 17 used to report AEs for Part A and B.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Part A: Olaparib - Fed	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were fed with high fat meal at breakfast time in both periods.
Part A: Olaparib - Fasted	Participants received a single olaparib 300 mg tablet orally on Day 1 in each of 2 treatment periods with at least 5 days and no more than 14 days of washout period between periods. Participants were overnight fasted in both periods.
Part B: Olaparib	Eligible participants received olaparib 300 mg tablets orally twice daily for 5 days.
Part C: Olaparib	Eligible participants continued to receive olaparib 300 mg tablets orally twice daily for 12 months.

Other Adverse Events

Part A: Olaparib - Fed

Part A: Olaparib - Fasted

Part B: Olaparib

Part C: Olaparib

Total, other (not including serious) adverse events

# participants affected / at risk

26/60 (43.33%)

33/60 (55.00%)

34/60 (56.67%)

51/60 (85.00%)

NERVOUS SYSTEM DISORDERS

DYSGEUSIA¹,^†

# participants affected / at risk

1/60 (1.67%)

0/60 (0.00%)

4/60 (6.67%)

7/60 (11.67%)

# events

NERVOUS SYSTEM DISORDERS

HEADACHE¹,^†

# participants affected / at risk

2/60 (3.33%)

5/60 (8.33%)

2/60 (3.33%)

4/60 (6.67%)

# events

PSYCHIATRIC DISORDERS

INSOMNIA¹,^†

# participants affected / at risk

0/60 (0.00%)

5/60 (8.33%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

COUGH¹,^†

# participants affected / at risk

0/60 (0.00%)

2/60 (3.33%)

0/60 (0.00%)

9/60 (15.00%)

# events

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

DYSPNOEA¹,^†

# participants affected / at risk

0/60 (0.00%)

4/60 (6.67%)

1/60 (1.67%)

8/60 (13.33%)

# events

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN¹,^†

# participants affected / at risk

2/60 (3.33%)

4/60 (6.67%)

1/60 (1.67%)

5/60 (8.33%)

# events

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN UPPER¹,^†

# participants affected / at risk

3/60 (5.00%)

0/60 (0.00%)

4/60 (6.67%)

# events

BLOOD AND LYMPHATIC SYSTEM DISORDERS

ANAEMIA¹,^†

# participants affected / at risk

3/60 (5.00%)

2/60 (3.33%)

1/60 (1.67%)

13/60 (21.67%)

# events

GASTROINTESTINAL DISORDERS

ASCITES¹,^†

# participants affected / at risk

2/60 (3.33%)

0/60 (0.00%)

1/60 (1.67%)

5/60 (8.33%)

# events

GASTROINTESTINAL DISORDERS

CONSTIPATION¹,^†

# participants affected / at risk

0/60 (0.00%)

2/60 (3.33%)

0/60 (0.00%)

7/60 (11.67%)

# events

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

5/60 (8.33%)

2/60 (3.33%)

4/60 (6.67%)

8/60 (13.33%)

# events

GASTROINTESTINAL DISORDERS

DRY MOUTH¹,^†

# participants affected / at risk

1/60 (1.67%)

4/60 (6.67%)

# events

GASTROINTESTINAL DISORDERS

GASTROOESOPHAGEAL REFLUX DISEASE¹,^†

# participants affected / at risk

0/60 (0.00%)

4/60 (6.67%)

# events

GASTROINTESTINAL DISORDERS

NAUSEA¹,^†

# participants affected / at risk

5/60 (8.33%)

11/60 (18.33%)

19/60 (31.67%)

# events

GASTROINTESTINAL DISORDERS

VOMITING¹,^†

# participants affected / at risk

3/60 (5.00%)

10/60 (16.67%)

7/60 (11.67%)

19/60 (31.67%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

FATIGUE¹,^†

# participants affected / at risk

6/60 (10.00%)

1/60 (1.67%)

5/60 (8.33%)

19/60 (31.67%)

# events

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

OEDEMA PERIPHERAL¹,^†

# participants affected / at risk

0/60 (0.00%)

2/60 (3.33%)

0/60 (0.00%)

7/60 (11.67%)

# events

INFECTIONS AND INFESTATIONS

URINARY TRACT INFECTION¹,^†

# participants affected / at risk

0/60 (0.00%)

4/60 (6.67%)

# events

METABOLISM AND NUTRITION DISORDERS

DECREASED APPETITE¹,^†

# participants affected / at risk

1/60 (1.67%)

3/60 (5.00%)

1/60 (1.67%)

16/60 (26.67%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

ARTHRALGIA¹,^†

# participants affected / at risk

2/60 (3.33%)

0/60 (0.00%)

2/60 (3.33%)

6/60 (10.00%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

BACK PAIN¹,^†

# participants affected / at risk

1/60 (1.67%)

0/60 (0.00%)

5/60 (8.33%)

# events

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

FLANK PAIN¹,^†

# participants affected / at risk

0/60 (0.00%)

4/60 (6.67%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 17.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

D0816C00004_Study_Synopsis_Redacted.pdf
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D0816C00004_food_effect_tablet_protocol_redacted_SECURE
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D0816C00004_Study_Synopsis_Redacted.pdf
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Trial Results Summaries
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Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

Malgorzata Szczodrak

malgorzata.szczodrak@astrazeneca.com

Investigators

Principal Investigator

Anitra Fielding

AstraZeneca Sponsor Research Physician

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

D0816C00004_Study_Synopsis_Redacted.pdf

D0816C00004_food_effect_tablet_protocol_redacted_SECURE

D0816C00004_Study_Synopsis_Redacted.pdf

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Trial Results Summaries

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