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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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
干预措施: Olaparib tablet dosing (Drug)
Mild hepatic impairment
As defined by the Child-Pugh Classification System.
干预措施: Olaparib tablet dosing (Drug)
Moderate hepatic impairment
As defined by the Child-Pugh Classification System.
干预措施: Olaparib tablet dosing (Drug)
结局指标
主要结局
Ratio of Maximum Plasma Concentration (Cmax) - Mild vs Normal and Moderate vs Normal
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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
次要结局
未报告次要终点