Study to Determine the Effect of Food on the Blood Levels of AZD9291 Following Oral Dosing of a Tablet Formulation in Patients With Non-Small Cell Lung Cancer

Phase 1

Completed

Conditions: Advanced Non Small Cell Lung Cancer
Advanced (Inoperable) Non Small Cell Lung Cancer

Interventions: Drug: AZD9291 tablets
Procedure: Pharmacokinetic sampling - AZD9291
Other: Dietary Fasted
Other: Dietary High Fat
Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

Registration Number: NCT02163733

Lead Sponsor: AstraZeneca

Brief Summary: This is a 2-part study in patients with epidermal growth factor receptor mutation positive (EGFRm+) non-small cell lung cancer (NSCLC) whose disease has progressed on treatment with an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI): Part A will determine the effect of food on the pharmacokinetics (PK) of AZD9291; Part B will allow patients further access to AZD9291 and will provide for additional safety data collection.

Part A is a randomised, open-label, 2 treatment period crossover study in which patients will each receive a single oral dose of AZD9291 (1 x 80 mg tablet) at breakfast time (approximately 0800) in each of 2 treatment periods (once immediately following a high fat meal \[fed\], and once in the fasted state \[fasted\]), with a washout period of 9 days between doses.

Approximately 38 patients are planned to be enrolled and dosed; at least 30 evaluable patients will be required to complete Part A (ie, the last PK sample in Treatment Period 2 \[TP 2\] has been collected). Additional patients may be enrolled to allow for at least 30 evaluable patients

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Fasted	AZD9291 tablets	AZD9291 tablets following a period of fasting
Fasted	Pharmacokinetic sampling - AZD9291	AZD9291 tablets following a period of fasting
Fasted	Dietary Fasted	AZD9291 tablets following a period of fasting
Fasted	Pharmacokinetic sampling - AZ5140 and AZ7550	AZD9291 tablets following a period of fasting
High-fat meal	AZD9291 tablets	AZD9291 tablets following a high-fat meal.
High-fat meal	Pharmacokinetic sampling - AZD9291	AZD9291 tablets following a high-fat meal.
High-fat meal	Dietary High Fat	AZD9291 tablets following a high-fat meal.
High-fat meal	Pharmacokinetic sampling - AZ5140 and AZ7550	AZD9291 tablets following a high-fat meal.

Primary Outcome Measures

Name	Time	Method
AUC(0-72) of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 72 hours.
Cmax of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration.

Secondary Outcome Measures

Name	Time	Method
AUC(0-t) of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Area under the plasma concentration curve from time zero to last quantifiable dose.
AUC(0-120) of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 120 hours.
Tmax of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of time to Cmax.
AUC(0-t) of AZ5104 and AZ7550	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Area under the plasma concentration curve from time zero to last quantifiable dose for AZ5104 and AZ7550 (metabolites to AZD9291).
Tmax of AZ5104 and AZ7550	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ5104 and AZ7550 (metabolites to AZD9291) by assessment of time to Cmax.
AUC of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Area under the plasma concentration curve from zero extrapolated to infinity.
t1/2 of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of the terminal half-life.
AUC(0-72) of AZ5104 and AZ7550	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ5104 and AZ7550 (metabolites to AZD9291) by assessment of area under the plasma concentration time curve from zero to 72 hours.
Cmax of AZ5104 and AZ7550	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ5104 and AZ7550 (metabolites to AZD9291) by assessment of maximum plasma concentration.
CL/F of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Rate and extent of absorption of AZD9291 by assessment of apparent clearance following oral administration.
Vz/F of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Rate and extent of absorption of AZD9291 by assessment of the apprarent volume of distribution.
t1/2 of AZ5104 and AZ7550	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ5104 and AZ7550 (metabolites to AZD9291) by assessment of the terminal half-life.
AUC(0-120) of AZ5104 and AZ7550	Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ5104 and AZ7550 (metabolites to AZD9291) by assessment of area under the plasma concentration time curve from zero to 120 hours.