Study to Assess the Effect of AZD9291 on the Blood Levels of Simvastatin in Patients With EGFRm+ NSCLC

Phase 1

Completed

• Conditions: Non Small Cell Lung Cancer
• Interventions: Procedure: Pharmacokinetic sampling - AZD9291; Drug: Simvastatin; Drug: AZD9291 tablet dosing; Procedure: Pharmacokinetic sampling - simvastatin; Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

• Registration Number: NCT02197234
• Lead Sponsor: AstraZeneca

Brief Summary

This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent.

Part A will assess the effect of AZD9291 on the pharmacokinetic (PK) parameters of simvastatin and simvastatin acid, following multiple oral dosing of AZD9291 in a fasted state.

Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients from Part A who completed treatment may continue to receive AZD9291 80 mg once daily until: disease progression; they are no longer deriving clinical benefit; or any other reason.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-07-21
• Study First Submitted QC: 2014-07-21
• Study First Posted: 2014-07-22
• Study Start: 2014-12-22
• Primary Completion: 2015-04-30
• Results First Submitted: 2016-04-08
• Results First Submitted QC: 2016-05-16
• Results First Posted: 2016-06-22
• Study Completion: 2024-06-03
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-02
• Last Update Posted: 2024-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
AZD9291 and simvastatin	Pharmacokinetic sampling - AZD9291	Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
AZD9291 and simvastatin	Simvastatin	Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
AZD9291 and simvastatin	AZD9291 tablet dosing	Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
AZD9291 and simvastatin	Pharmacokinetic sampling - simvastatin	Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.
AZD9291 and simvastatin	Pharmacokinetic sampling - AZ5140 and AZ7550	Sequential treatments of simvastatin alone followed by AZD9291 alone, followed by simvastatin + AZD9291.

Primary Outcome Measures

Name	Time	Method
Cmax of Simvastatin	Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A	Pharmacokinetics of simvastatin by assessment of maximum plasma simvastatin concentration
AUC of Simvastatin	Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A	Pharmacokinetics of simvastatin by assessment of area under the plasma concentration time curve from zero to infinity

Secondary Outcome Measures

Name	Time	Method
Tmax of Simvastatin and Simvastatin Acid	Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A	Pharmacokinetics of simvastatin and simvastatin acid by time to Cmax
CL/F of Simvastatin	Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A	Rate and extent of absorption of simvastatin by assessment of apparent clearance following oral administration
Cmax of Simvastatin Acid	Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A	Pharmacokinetics of simvastatin acid by assessment of maximum plasma simvastatin acid concentration
AUC of Simvastatin Acid	Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A	Pharmacokinetics of simvastatin acid by assessment of area under the plasma concentration time curve from zero to infinity
AUC(0-t) of Simvastatin and Simvastatin Acid	Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part A	Pharmacokinetics of simvastatin and simvastatin acid by assessment of area under the plasma concentration time curve from time zero to last quantifiable dose

Trial Locations

Locations (1)

Research Site; 🇪🇸 Sevilla, Spain