A 2-Part Study to Assess Potential Metabolism-Based Drug-Drug Interactions of E2006 When Coadministered With Itraconazole, Rifampin, Midazolam, or Bupropion

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: rifampin 600 mg; Drug: midazolam 2 mg with bupropion 75 mg; Drug: itraconazole 200 mg; Drug: E2006

• Registration Number: NCT02085967
• Lead Sponsor: Eisai Inc.

Brief Summary

This study will be a single center, open-label, drug-drug interaction study in healthy male and female subjects. The study will consist of 2 parts. In Part A, the effects of steady-state dosing of a strong CYP3A inhibitor (itraconazole) or inducer (rifampin) on the pharmacokinetics of E2006 and metabolites will be assessed. Approximately 30 subjects will be sequentially assigned to 1 of 2 treatment groups to receive itraconazole or rifampin in equal numbers (approximately 15 subjects per group). The itraconazole treatment group will be fully enrolled before enrollment is initiated for the rifampin treatment group. In Part B, the effects of steady-state dosing of E2006 on the pharmacokinetics of midazolam, a substrate of CYP3A, plus bupropion, a substrate of CYP2B6, will be assessed in approximately 24 subjects. The 2 study parts can be conducted in parallel.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-03-10
• Study First Submitted QC: 2014-03-11
• Study First Posted: 2014-03-13
• Primary Completion: 2014-04
• Study Completion: 2014-06
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-02
• Last Update Posted: 2015-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 106

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
E2006 Part A	rifampin 600 mg	E2006 10-mg tablets alone and in combination with rifampin 600 mg or itraconazole 200 mg
E2006 Part A	itraconazole 200 mg	E2006 10-mg tablets alone and in combination with rifampin 600 mg or itraconazole 200 mg
E2006 Part B	midazolam 2 mg with bupropion 75 mg	E2006 10-mg tablets alone and in combination with midazolam 2 mg plus bupropion 75 mg
E2006 Part B	E2006	E2006 10-mg tablets alone and in combination with midazolam 2 mg plus bupropion 75 mg
E2006 Part A	E2006	E2006 10-mg tablets alone and in combination with rifampin 600 mg or itraconazole 200 mg

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): AUC(0-t)	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Area under the concentration-time curve from zero time to time of last quantifiable concentration
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): AUC(0-inf)	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Area under the concentration-time curve from zero time extrapolated to infinite time
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): Cmax	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Maximum observed concentration

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): tmax	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Time at which the highest drug concentration occurs
Pharmacokinetics of E2006: AUC(0-8h)	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Area under the concentration-time curve from time zero time to 8 hours after dosing (E2006 only)
Pharmacokinetics of E2006: AUC(0-24h)	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Area under the concentration-time curve from time zero time to 24 hours after dosing (E2006 only)
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): AUC(0-72h)	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Area under the concentration-time curve from zero time to time 72 hours after dosing
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): t1/2	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Terminal elimination phase half-life
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): CL/F	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Apparent total clearance after extravascular administration
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): AUC(0-inf), metabolite ratio	Approximately 56 Days for Part A; Approximately 42 Days for Part B	Ratio of S,S-hydroxybupropion to S-buproprion

Trial Locations

Locations (1)

PPD Development LLC; 🇺🇸 Austin, Texas, United States