A Pharmacokinetic Study to Assess the Influence of Simultaneous CYP3A4 and P-glycoprotein Inhibition on E7080 Pharmacokinetics Following Single Dose Oral Administration of 5 mg E7080 to Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: placebo-ketoconazole; Drug: ketoconazole-placebo

• Registration Number: NCT02198170
• Lead Sponsor: Eisai Inc.

Brief Summary

The purpose of this study is to assess the influence of simultaneous CYP3A4 and p-glycoprotein inhibition on lenvatinib pharmacokinetics following a single oral dose of 5 mg lenvatinib.

Detailed Description

This is a single-center, randomized, open-label, two-period, crossover study consisting of two phases: Prerandomization and Randomization. The Prerandomization Phase will have two periods: Screening and Baseline 1. The Randomization Phase will have two periods: Treatment Period 1 and Treatment Period 2 with a Baseline 2 assessment prior to Treatment Period 2. In the Randomization Phase, subjects will be randomized to one of two possible treatment sequences (placebo/ketoconazole or ketoconazole/placebo). Ketoconazole 400 mg or placebo will be orally administered once daily for the first four days of each treatment period. On the fifth day of each treatment period, in addition to ketoconazole/placebo, 5 mg lenvatinib will be orally administered. Ketoconazole/placebo administration will then continue for 13 additional days. Subjects are crossed over from Treatment Period 1 to Treatment Period 2 after a 2-week washout.

Study Timeline

• Study Start: 2011-02
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Study First Submitted: 2014-07-21
• Study First Submitted QC: 2014-07-22
• Study First Posted: 2014-07-23
• Status Verified: 2015-01
• Last Update Submitted: 2015-02-11
• Last Update Posted: 2015-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
placebo-ketoconazole	placebo-ketoconazole	Treatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period
ketoconazole-placebo	ketoconazole-placebo	Treatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-inf)	Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: Cmax	Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-t)	Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose

Secondary Outcome Measures

Name	Time	Method
Safety as Measured by Outcome of Adverse Events	Screening, Up to Day 52
Safety as Measured by Physical Examination	Screening, Up to Day 52
Safety as Measured by Laboratory Values	Screening, Up to Day 52
Safety as Measured by Vital Signs	Screening, Up to Day 52
Safety as Measured by ECGs	Screening, Up to Day 52