An Open-label, Non-randomised, Multicentre, Comparative, Phase I Study to Determine the Pharmacokinetics, Safety and Tolerability of AZD9291 Following a Single Oral 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
- 30
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration (Cmax)
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 pharmacokinetics (PK) of AZD9291 in patients with mild or moderate hepatic impairment compared to patients with normal hepatic function; Part B will allow any patient with mild or moderate hepatic impairment or normal hepatic function, who completes Part A, continued access to AZD9291 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 99 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 without a history or presence of hepatic disease
干预措施: AZD9291 tablet dosing (Drug)
Normal hepatic function
Patients without a history or presence of hepatic disease
干预措施: Pharmacokinetic sampling - AZD9291 (Procedure)
Normal hepatic function
Patients without a history or presence of hepatic disease
干预措施: Pharmacokinetic sampling - AZ5140 and AZ7550 (Procedure)
Mild hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh A
干预措施: AZD9291 tablet dosing (Drug)
Mild hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh A
干预措施: Pharmacokinetic sampling - AZD9291 (Procedure)
Mild hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh A
干预措施: Pharmacokinetic sampling - AZ5140 and AZ7550 (Procedure)
Moderate hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh B
干预措施: AZD9291 tablet dosing (Drug)
Moderate hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh B
干预措施: Pharmacokinetic sampling - AZD9291 (Procedure)
Moderate hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh B
干预措施: Pharmacokinetic sampling - AZ5140 and AZ7550 (Procedure)
结局指标
主要结局
Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration (Cmax)
时间窗: Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours
Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of maximum plasma AZD9291 concentration (Cmax).
Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to infinity (AUC)
时间窗: Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours
Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of area under the plasma concentration time curve from zero to infinity (AUC).
次要结局
- Pharmacokinetics of AZD9291, AZ5104, and AZ7550 by assessment of AUC(0-t)(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZ5104 and AZ7550 by assessment of Cmax(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Assessment of the safety and tolerability of AZD9291(Parts A and B, approximately seven months)
- Pharmacokinetics of AZD9291, AZ5104, and AZ7550 by assessment of tmax(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZD9291, AZ5104, and AZ7550 by assessment of AUC(0-24)(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZD9291, AZ5104, and AZ7550 by assessment of AUC(0-72)(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZD9291, AZ5104, and AZ7550 by assessment of AUC(0-168)(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZD9291, AZ5104, and AZ7550 by assessment of λz(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZD9291, AZ5104, and AZ7550 by assessment of t½(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZD9291, AZ5104, and AZ7550 by assessment of CL(R)(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZD9291 by assessment of CL/F(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZD9291 by assessment of Vz/F(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)
- Pharmacokinetics of AZ5104 and AZ7550 by assessment of AUC(Blood samples are collected at the following timepoints post AZD9291 dose on Day 1: pre-dose, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, and 504 hours)