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

Phase 1

Completed

• Conditions: Solid Tumours
• Interventions: Drug: Olaparib tablet dosing

• Registration Number: NCT01894243
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-07-04
• Study First Submitted QC: 2013-07-04
• Study First Posted: 2013-07-10
• Study Start: 2014-03-13
• Primary Completion: 2016-11-29
• Study Completion: 2017-03-30
• Results First Submitted: 2017-11-29
• Status Verified: 2019-07
• Results First Submitted QC: 2019-08-07
• Last Update Submitted: 2019-08-07
• Results First Posted: 2019-09-13
• Last Update Posted: 2019-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal hepatic function	Olaparib tablet dosing	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
Mild hepatic impairment	Olaparib tablet dosing	As defined by the Child-Pugh Classification System.
Moderate hepatic impairment	Olaparib tablet dosing	As defined by the Child-Pugh Classification System.

Primary Outcome Measures

Name	Time	Method
Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.	Summary of ratio of Geometric Least Squares (GLS) Means
Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.	Summary of Geometric Least Squares (GLS) Mean
Ratio of Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC) - Mild vs Normal and Moderate vs Normal	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.	Summary of Ratio of Geometric Least Squares (GLS) Means
Area Under the Plasma Concentration Time Curve From Zero to the Last Measureable Time Point(AUC 0-t)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.	Summary of Geometric Least Squares (GLS) Mean for ratio of mild hepatic impairment compared to normal
Ratio of Area Under the Plasma Concentration Time Curve From Zero to the Last Measureable Time Point(AUC 0-t)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.	Summary of Ratio of Geometric Least Squares (GLS) Means
Apparent Clearance Following Oral Administration (CL/F)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.	Summary of Geometric Least Squares (GLS) Means
Ratio of Apparent Clearance Following Oral Administration (CL/F)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.	Summary of Ratio of Geometric Least Squares (GLS) Means
Time to Reach Maximum Plasma Concentration (Tmax)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Terminal Half-life (t½)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Apparent Volume of Distribution (Vz/F)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.
Maximum Plasma Concentration (Cmax)	Blood samples are collected at pre-dose, 0.25 , 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post olaparib dose in Part A.	Summary of Geometric Least Squares (GLS) Mean for normal, mild and moderate hepatic impairment

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sutton, United Kingdom