Study to Assess the Blood Levels and Safety of AZD9291 in Patients With Advanced Solid Tumours and Normal Liver Function or Mild or Moderate Liver Impairment

Phase 1

Completed

• Conditions: Solid Tumours
• Interventions: Drug: AZD9291 tablet dosing; Procedure: Pharmacokinetic sampling - AZD9291; Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

• Registration Number: NCT02161770
• Lead Sponsor: AstraZeneca

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-05-29
• Study First Submitted QC: 2014-06-10
• Study First Posted: 2014-06-12
• Study Start: 2014-12-22
• Primary Completion: 2017-05-16
• Study Completion: 2017-08-22
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-07
• Last Update Posted: 2019-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal hepatic function	AZD9291 tablet dosing	Patients without a history or presence of hepatic disease
Normal hepatic function	Pharmacokinetic sampling - AZD9291	Patients without a history or presence of hepatic disease
Normal hepatic function	Pharmacokinetic sampling - AZ5140 and AZ7550	Patients without a history or presence of hepatic disease
Mild hepatic impairment	AZD9291 tablet dosing	Patients defined by the Child-Pugh classification system to be Child-Pugh A
Moderate hepatic impairment	AZD9291 tablet dosing	Patients defined by the Child-Pugh classification system to be Child-Pugh B
Mild hepatic impairment	Pharmacokinetic sampling - AZD9291	Patients defined by the Child-Pugh classification system to be Child-Pugh A
Mild hepatic impairment	Pharmacokinetic sampling - AZ5140 and AZ7550	Patients defined by the Child-Pugh classification system to be Child-Pugh A
Moderate hepatic impairment	Pharmacokinetic sampling - AZD9291	Patients defined by the Child-Pugh classification system to be Child-Pugh B
Moderate hepatic impairment	Pharmacokinetic sampling - AZ5140 and AZ7550	Patients defined by the Child-Pugh classification system to be Child-Pugh B

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration (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	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)	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 Outcome Measures

Name	Time	Method
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	Rate and extent of absorption of AZD9291 by assessment of AUC from time zero to last quantifiable dose AUC(0-t)
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 PK of AZ5104 and AZ7550 using maximum plasma concentration (Cmax).
Assessment of the safety and tolerability of AZD9291	Parts A and B, approximately seven months	Safety data collected using: Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0; Vital signs (blood pressure, pulse, temperature, height, weight); laboratory parameters (clinical chemistry, haematology, urinalysis); physical examination; and standard 12-lead electrocardiograms (ECGs)
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	Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of time to Cmax (tmax)
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	Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of AUC from time zero to t=24, AUC(0-24)
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	Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of AUC from time zero to t=72, AUC(0-72)
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	Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of AUC from time zero to t=168, AUC(0-168).
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	Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of terminal rate constant (λz).
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	Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of the terminal half-life (t1/2).
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	Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of renal clearance (CL(R).
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	Rate and extent of absorption of AZD9291 by assessment of the apparent clearance following oral administration (CL/F)
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	Rate and extent of absorption of AZD9291 by assessment of the apparent volume of distribution (Vz/F)
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	Assessment of the PK of AZ5104 and AZ7550 using area under the plasma concentration curve from zero extrapolated to infinity (AUC).

Trial Locations

Locations (1)

Research Site; 🇬🇧 Newcastle Upon Tyne, United Kingdom