Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Renal Insufficiency

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients with calculated serum creatinine clearance ≥81 mL/min (using Cockcroft-Gault equation).

Patients with calculated serum creatinine clearance 51-80 mL/min (using Cockcroft-Gault equation).

Patients with calculated serum creatinine clearance 31-50 mL/min (using Cockcroft-Gault equation).

Part A - single 300mg oral dose olaparib (administered as 2x150mg tablets) Part B - 300mg oral dose olaparib (administered as 2x150mg tablets) bd

Olaparib tablet dosing

Anitra Fielding

Christian Rolfo

This is a 2-part study in patients with advanced solid tumours. Part A will investigate the PK of olaparib in patients with mild or moderate renal impairment compared to patients with normal renal function; Part B will allow eligible study patients continued access to olaparib after the PK phase and will provide additional safety data.

Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal or Impaired Kidney Function

An Open-label, Non-randomised, Multicentre, Comparative, Phase I Study of the Pharmacokinetics, Safety and Tolerability of Olaparib Following a Single Oral 300 mg Dose to Patients With Advanced Solid Tumours and Normal Renal Function or Renal Impairment

Degree to which olaparib binds to the proteins within blood plasma

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

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

Maximum plasma drug concentration of olaparib

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

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

Time to reach maximum plasma concentration of olaparib

Apparent volume of distribution of olaparib

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

AstraZeneca

AE data were collected on Days 1-5, and at 30 days following the date of last dose of study medication if the subject discontinued in Part A.

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).

Part A Normal Renal Function

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).

Part A Mild 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).

Part A Moderate Renal Impairment

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).

Part B Normal Renal Function

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).

Part B Mild 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).

Part B Moderate Renal Impairment

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).

Normal Renal Function

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).

Mild 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).

Moderate Renal Impairment

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Data are presented for Part A and Part B.

Dr Anitra Fielding

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.

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.

Cmax of Olaparib

AUC of Olaparib

AUC0-t of Olaparib

Tmax of Olaparib

Vz/F of Olaparib

CL/F of Olaparib

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.

CLR of Olaparib

t1/2 of Olaparib

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.

Spots Global Cancer Trial Database for mild renal impairment,