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
Overview
- Phase
- Phase 1
- Intervention
- AZD9291 tablet dosing
- Conditions
- Solid Tumours
- Sponsor
- AstraZeneca
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration (Cmax)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Normal hepatic function
Patients without a history or presence of hepatic disease
Intervention: AZD9291 tablet dosing
Normal hepatic function
Patients without a history or presence of hepatic disease
Intervention: Pharmacokinetic sampling - AZD9291
Normal hepatic function
Patients without a history or presence of hepatic disease
Intervention: Pharmacokinetic sampling - AZ5140 and AZ7550
Mild hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh A
Intervention: AZD9291 tablet dosing
Mild hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh A
Intervention: Pharmacokinetic sampling - AZD9291
Mild hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh A
Intervention: Pharmacokinetic sampling - AZ5140 and AZ7550
Moderate hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh B
Intervention: AZD9291 tablet dosing
Moderate hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh B
Intervention: Pharmacokinetic sampling - AZD9291
Moderate hepatic impairment
Patients defined by the Child-Pugh classification system to be Child-Pugh B
Intervention: Pharmacokinetic sampling - AZ5140 and AZ7550
Outcomes
Primary Outcomes
Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration (Cmax)
Time Frame: 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)
Time Frame: 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).
Secondary Outcomes
- 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)