Study to Assess the Blood Levels and Safety of Olaparib i... | NCT01894256

ID	Type	Description	Link
2013-002225-30	EudraCT Number

Label	Type	Description	Intervention Names
Normal renal function	Other	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation).	Drug: Olaparib tablet dosing
Mild renal impairment	Other	Patients with calculated serum creatinine clearance 51-80 mL/min (using Cockcroft-Gault equation).	Drug: Olaparib tablet dosing
Moderate renal impairment	Other	Patients with calculated serum creatinine clearance 31-50 mL/min (using Cockcroft-Gault equation).	Drug: Olaparib tablet dosing

Name	Type	Description	Arm Group Labels	Other Names
Olaparib tablet dosing	Drug	Part A - single 300mg oral dose olaparib (administered as 2x150mg tablets) Part B - 300mg oral dose olaparib (administered as 2x150mg tablets) bd	Mild renal impairment

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cmax of Olaparib	Maximum plasma drug concentration of olaparib	Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
AUC of Olaparib	Area under plasma concentration-time curve from zero to infinity of olaparib	Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
AUC0-t of Olaparib	Area under plasma concentration-time curve from zero to the last measurable time point of olaparib	Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Tmax of Olaparib	Time to reach maximum plasma concentration of olaparib	Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Vz/F of Olaparib	Apparent volume of distribution of olaparib	Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
CL/F of Olaparib	Apparent plasma clearance of olaparib	Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
CLR of Olaparib	Renal clearance of olaparib, calculated as the ratio of amount of drug excreted over 24 hours to AUC0-24	Part A: Day 1, 0-12 hours and 12-24 hours post-dose

Other Outcomes

Measure	Description	Time Frame
Protein Binding of Olaparib	Degree to which olaparib binds to the proteins within blood plasma	Part A: Day 1, 1 hour post-dose
Free Cmax of Olaparib	Cmax of unbound olaparib; calculated by multiplying total Cmax value by estimated protein binding

Eligibility Module

Eligibility Criteria

Inclusion criteria:-

For inclusion in the study as a patient with renal impairment, the following criterion must be met:

Patients must have stable renal impairment (moderate or mild), depending on creatinine clearance estimated using the Cockcroft-Gault equation (moderate 31 to 50 mL/min; mild 51 to 80 mL/min), for at least 2 months prior to the start of the study. For inclusion in the study as a patient with normal renal function, the following criterion must be met:
Calculated serum creatinine clearance greater than or equal to 81 mL/min (using Cockcroft-Gault equation). All patients must fulfil the following criteria:
Provision of written informed consent prior to any study specific procedures .
Patients must be greater than or equal to 18 and less than or equal to 75 years of age.
Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.
BMI between 18-30 kg/m2.
Normal liver and bone marrow function measured within 28 days prior to administration of IP as defined below: Haemoglobin (Hb) 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 or serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase or serum glutamic pyruvic transaminase (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 5x ULN.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Patients must have a life expectancy greater than or equal to 12 weeks.
Evidence of non childbearing status for women of childbearing potential, or postmenopausal 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 postmenopausal 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).
Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
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:-

Patients must not enter the study if any of the following exclusion criteria are fulfilled:

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, its agents and/or staff at the study site).
Previous enrolment in the present study.
Participation in another clinical study with an investigational medicinal product (IP) during the last 14 days (or a longer period depending on the defined characteristics of the agent used).
Renal transplant and end stage renal disease (ESRD) patients.
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.
Patients who have received or are receiving inhibitors or inducers of CYP3A4 within the washout period.
For Part A only, drugs which affect creatinine clearance such as cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine and quinine should not be used within the 7 days prior to dosing with olaparib.
Treatment in the previous 3 months with any drug known to have a well-defined potential for hepatotoxicity (eg, halothane).
Persistent toxicities (greater than or equal to CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia.
Patients with myelodysplastic syndrome/acute myeloid leukaemia.
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.
Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of major surgery.
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 computer tomography (HRCT) scan, or any psychiatric disorder that prohibits obtaining informed consent.
Patients with a history of heart failure or left ventricular dysfunction.
Patients who have gastric, gastro-oesophageal or oesophageal cancer.
Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of olaparib.
Breastfeeding women.
Immunocompromised patients eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
Patients with known active hepatic disease (eg, hepatitis B or C).
Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
Resting ECG at screening with measurable QTc greater than 470 msec at 2 or more time points within a 24 hour period or family history of long QT syndrome.
Clinical judgment by the investigator that the patient should not participate in the study.

Name	Affiliation	Role
Anitra Fielding	AstraZeneca Senior Research Physician	Study Director
Christian Rolfo	UZ Antwerpen	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Brussels (Jette)			Belgium
Research Site

PubMed Identifier	Type	Citation	Retractions
30877569	Derived	Rolfo C, de Vos-Geelen J, Isambert N, Molife LR, Schellens JHM, De Greve J, Dirix L, Grundtvig-Sorensen P, Jerusalem G, Leunen K, Mau-Sorensen M, Plummer R, Learoyd M, Bannister W, Fielding A, Ravaud A. Pharmacokinetics and Safety of Olaparib in Patients with Advanced Solid Tumours and Renal Impairment. Clin Pharmacokinet. 2019 Sep;58(9):1165-1174. doi: 10.1007/s40262-019-00754-4.

ID	Title	Description
FG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
FG001	Mild Renal Impairment

ID	Title	Description
BG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
BG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
BG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00015 BG00115 BG00214 BG00344

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

Cmax of Olaparib

Maximum plasma drug concentration of olaparib

PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Units	Counts
Participants	OG00012 OG00113 OG00213

Title

Denominators

Categories

Title	Measurements
	OG0007.227± 31.0 OG0019.081± 40.6 OG0029.977± 44.2

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	Null hypothesis: There are no clinically significant differences in the PK of olaparib when administered to patients with moderate or mild renal impairment compared to patients with normal renal function.					Geometric least squares means ratio	1.15			2-Sided	90	1.04	1.27			GLS mean for Mild Renal Impairment group vs GLS mean for Normal Renal Function	No	Superiority or Other

Primary

AUC of Olaparib

Area under plasma concentration-time curve from zero to infinity of olaparib

PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg*h/mL

Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Primary

AUC0-t of Olaparib

Area under plasma concentration-time curve from zero to the last measurable time point of olaparib

PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg*h/mL

Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Primary

Tmax of Olaparib

Time to reach maximum plasma concentration of olaparib

PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Median

Full Range

Hours

Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Primary

Vz/F of Olaparib

Apparent volume of distribution of olaparib

PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Mean

Standard Deviation

Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Primary

CL/F of Olaparib

Apparent plasma clearance of olaparib

PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Mean

Standard Deviation

L/hour

Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Primary

CLR of Olaparib

Renal clearance of olaparib, calculated as the ratio of amount of drug excreted over 24 hours to AUC0-24

Subset of PK analysis set with urine samples available. PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Mean

Standard Deviation

L/hour

Part A: Day 1, 0-12 hours and 12-24 hours post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Primary

t1/2 of Olaparib

Terminal half-life of olaparib

PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Mean

Standard Deviation

Hours

Part A: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Other Pre-specified

Protein Binding of Olaparib

Degree to which olaparib binds to the proteins within blood plasma

Subset of PK analysis set with protein binding blood sample available. PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Mean

Standard Deviation

% plasma

Part A: Day 1, 1 hour post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Other Pre-specified

Free Cmax of Olaparib

Cmax of unbound olaparib; calculated by multiplying total Cmax value by estimated protein binding

Subset of PK analysis set with protein binding blood sample available. PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

Part A: Day 1, 1 hour post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment

Other Pre-specified

Free AUC of Olaparib

AUC of unbound olaparib; calculated by multiplying total AUC by estimated protein binding

Subset of PK analysis set with protein binding blood sample available. PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg*h/mL

Part A: Day 1, 1 hour post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment

Other Pre-specified

CL/F of Unbound Olaparib

Calculated from dose divided by free AUC

Subset of PK analysis set with protein binding blood sample available. PK analysis set: All patients who receive an olaparib dose and have full PK sampling up to 96 hours post-dose.

Any patients with major protocol deviations that affected the evaluability of the PK profile were excluded.

Posted

Median

Standard Deviation

L/hour

Part A: Day 1, 1 hour post-dose

ID	Title	Description
OG000	Normal Renal Function	Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG001	Mild Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).
OG002	Moderate Renal Impairment	Patients with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A Normal Renal Function	Patients from Part A of the study with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).	0	15	10	15
EG001	Part A Mild Renal Impairment	Patients in Part A of the study with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).	1	15	11	15
EG002	Part A Moderate Renal Impairment	Patients in Part A of the study with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).	0	14	6	14
EG003	Part B Normal Renal Function	Patients in Part B of the study with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation). Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).	3	15	15	15
EG004	Part B Mild Renal Impairment	Patient in Part B of the study with stable renal impairment with calculated serum creatinine clearance 51 to 80 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).	3	14	14	14
EG005	Part B Moderate Renal Impairment	Patient in Part B of the study with stable renal impairment with calculated serum creatinine clearance 31 to 50 mL/min (using Cockcroft-Gault equation), for at least 2 months prior to the start of the study. Received single dose of 300 mg olaparib (2 x 150 mg tablets) in fasted condition (1 hour before their olaparib dose until 2 hours after dosing).	3	14	14	14

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ASTHENIA	General disorders	MedDRA version 18.0	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected15 at risk EG0020 events0 affected14 at risk EG0030 events0 affected15 at risk EG0040 events0 affected14 at risk EG0050 events0 affected14 at risk
ANAEMIA	Blood and lymphatic system disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
URINARY TRACT INFECTION	Infections and infestations	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
CONFUSIONAL STATE	Psychiatric disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
ILEUS	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
NON CARDIAC CHEST PAIN	General disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
INFECTION	Infections and infestations	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
UROSEPSIS	Infections and infestations	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
HYPONATRAEMIA	Metabolism and nutrition disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
INTERVERTEBRAL DISC DEGENERATION	Musculoskeletal and connective tissue disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0022 affected14 at risk EG0033 affected15 at risk EG0045 affected14 at risk EG0055 affected14 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0012 affected15 at risk EG0020 affected14 at risk EG003
CONSTIPATION	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected15 at risk EG0022 affected14 at risk EG003
NAUSEA	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0003 affected15 at risk EG0012 affected15 at risk EG0020 affected14 at risk EG003
VOMITING	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0012 affected15 at risk EG0020 affected14 at risk EG003
ASTHENIA	General disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0021 affected14 at risk EG003
FATIGUE	General disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0021 affected14 at risk EG003
PYREXIA	General disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk EG003
URINARY TRACT INFECTION	Infections and infestations	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk EG003
HYPERGLYCAEMIA	Metabolism and nutrition disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
HYPONATRAEMIA	Metabolism and nutrition disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
MUSCULOSKELETAL PAIN	Musculoskeletal and connective tissue disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk EG003
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
ALTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
DYSGEUSIA	Nervous system disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk EG003
CONFUSIONAL STATE	Psychiatric disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
DYSURIA	Renal and urinary disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
RENAL FAILURE	Renal and urinary disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk EG003
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected15 at risk EG0020 affected14 at risk EG003
RASH	Skin and subcutaneous tissue disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA version 18.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
DIARRHOEA	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
DYSPEPSIA	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
NON CARDIAC CHEST PAIN	General disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
ODEMA PERIPHERAL	General disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
WEIGHT DECREASED	Investigations	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
HYPERCALCAEMIA	Metabolism and nutrition disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
HYPERKALAEMIA	Metabolism and nutrition disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
CANCER PAIN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
TUMOUR PAIN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
HEADACHE	Nervous system disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003
DYSPNOEA EXERTIONAL	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected15 at risk EG0020 affected14 at risk EG003