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
Overview
- Phase
- Phase 1
- Intervention
- Olaparib tablet dosing
- Conditions
- Solid Tumours
- Sponsor
- AstraZeneca
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Normal hepatic function
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
Intervention: Olaparib tablet dosing
Mild hepatic impairment
As defined by the Child-Pugh Classification System.
Intervention: Olaparib tablet dosing
Moderate hepatic impairment
As defined by the Child-Pugh Classification System.
Intervention: Olaparib tablet dosing
Outcomes
Primary Outcomes
Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal
Time Frame: 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)
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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