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Patients with:

(i) negative result for serum hepatitis B surface antigen and hepatitis C antibody (ii) total bilirubin ≤1.5 x institutional upper limit of normal (ULN), albumin and prothrombin time within normal limits and must not have ascites (unless related to disease under study) or encephalopathy (iii) aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase or serum glutamic pyruvic transaminase (ALT) ≤2.5 x institutional ULN unless liver metastases are present in which case it must be ≤5 x ULN

As defined by the Child-Pugh Classification System.

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 hepatic impairment compared to patients with normal hepatic function; Part B will allow patients with mild or moderate hepatic impairment or normal hepatic function 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 Liver Function or Mild or Moderate Liver Impairment

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

Summary of Geometric Least Squares (GLS) Mean for normal, mild and moderate hepatic impairment

Summary of ratio of Geometric Least Squares (GLS) Means

Summary of Geometric Least Squares (GLS) Mean

Summary of Ratio of Geometric Least Squares (GLS) Means

Summary of Geometric Least Squares (GLS) Mean for ratio of mild hepatic impairment compared to normal

Summary of Geometric Least Squares (GLS) Means

AstraZeneca

Normal (Part A)

Mild (Part A)

Moderate (Part A)

Normal (Part B)

Mild (Part B)

Moderate (Part B)

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with normal hepatic function

Normal Hepatic Function

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with mild hepatic function

Mild Hepatic Impairment

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with moderate hepatic function

Moderate Hepatic Impairment

Total

Age, Continuous

Sex: Female, Male

Anitra Fielding - Senior Research Physician

Moderate Hepatic Function

PK Analysis Set (Part A) One patient excluded from mild impairment arm due to surgery that may affect olaparib absorption.

Maximum Plasma Concentration (Cmax)

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with mild/normal hepatic function

GLSMean Ratio of Mild to Normal

Olaparib 300 mg (2x150 mg tablets) single dose administered to patients with moderate/normal hepatic function

GLSMean Ratio of Moderate to Normal

PK Analysis Set (Part A) One patient excluded from mild impairment group due to surgery that may affect olaparib absorption.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal Liver Function or Mild or Moderate Liver Impairment	NCT01894243	Solid Tumours	Olaparib tablet...	18 Years - 130 Years	AstraZeneca
Study to Assess the Blood Levels and Safety of Olaparib in Patients With Advanced Solid Tumours and Normal Liver Function or Mild or Moderate Liver Impairment	NCT01894243	Solid Tumours	Olaparib tablet...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for mild hepatic impairment,