Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Amino Acids

Osimertinib

Liver Extracts

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients without a history or presence of hepatic disease

Patients defined by the Child-Pugh classification system to be Child-Pugh A

Patients defined by the Child-Pugh classification system to be Child-Pugh B

Part A - single 80mg oral dose AZD9291 (administered as 1 80mg tablet). Part B - 80mg oral dose AZD9291 od.

AZD9291 tablet dosing

Blood sampling to measure AZD9291 pharmacokinetic parameters.

Pharmacokinetic sampling - AZD9291

Blood samples to measure the pharmacokinetic parameters of AZ5104 and AZ7550.

Pharmacokinetic sampling - AZ5140 and AZ7550

Yuri Rukazenkov

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.

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

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

Rate and extent of absorption of AZD9291 following single oral doses of AZD9291 tablet formulation by assessment of maximum plasma AZD9291 concentration (Cmax).

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).

Rate and extent of absorption of AZD9291 by assessment of AUC from time zero to last quantifiable dose AUC(0-t)

Assessment of the PK of AZ5104 and AZ7550 using maximum plasma concentration (Cmax).

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)

Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of time to Cmax (tmax)

Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of AUC from time zero to t=24, AUC(0-24)

Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of AUC from time zero to t=72, AUC(0-72)

Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of AUC from time zero to t=168, AUC(0-168).

Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of terminal rate constant (λz).

Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of the terminal half-life (t1/2).

Rate and extent of absorption of AZD9291, AZ5104, and AZ7550 by assessment of renal clearance (CL(R).

Rate and extent of absorption of AZD9291 by assessment of the apparent clearance following oral administration (CL/F)

Rate and extent of absorption of AZD9291 by assessment of the apparent volume of distribution (Vz/F)

Assessment of the PK of AZ5104 and AZ7550 using area under the plasma concentration curve from zero extrapolated to infinity (AUC).

Spots Global Cancer Trial Database for oncology, cancer, neoplasm, anticancer drug, pharmacokinetics, area under curve, azd9291, solid tumour, mild hepatic impairment, moderate hepatic impairment