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

NCT02085967 | Completed Phase 1

• 1 other identifier: E2006-A001-004
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

Healthy; Metabolism; Drug-Drug Interactions

Outcome Measures

Primary Outcomes (3)

• 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)

  Area under the concentration-time curve from zero time to time of last quantifiable concentration

  Approximately 56 Days for Part A; Approximately 42 Days for Part B

• 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)

  Area under the concentration-time curve from zero time extrapolated to infinite time

  Approximately 56 Days for Part A; Approximately 42 Days for Part B

• 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

  Maximum observed concentration

  Approximately 56 Days for Part A; Approximately 42 Days for Part B

Secondary Outcomes (7)

• 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

• Pharmacokinetics of E2006: AUC(0-8h)

  Approximately 56 Days for Part A; Approximately 42 Days for Part B

• Pharmacokinetics of E2006: AUC(0-24h)

  Approximately 56 Days for Part A; Approximately 42 Days for Part B

• 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

• 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

Study Arms (2)

E2006 Part A

EXPERIMENTAL

E2006 10-mg tablets alone and in combination with rifampin 600 mg or itraconazole 200 mg

Drug: rifampin 600 mg; Drug: itraconazole 200 mg; Drug: E2006

E2006 Part B

EXPERIMENTAL

E2006 10-mg tablets alone and in combination with midazolam 2 mg plus bupropion 75 mg

Drug: midazolam 2 mg with bupropion 75 mg; Drug: E2006

Interventions

rifampin 600 mg DRUG

E2006 Part A

itraconazole 200 mg DRUG

E2006 Part A

midazolam 2 mg with bupropion 75 mg DRUG

E2006 Part B

E2006 DRUG

E2006 Part A; E2006 Part B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must meet all of the following criteria to be included in this study:
• Healthy males or females, ages 18 to 55 years
• Body mass index greater than 18 and less than or equal to 32 kg/m2 at Screening
• All females must be of nonchildbearing potential
• Males who are not abstinent or have undergone a successful vasectomy, who are partners of women of childbearing potential must use, or their partners must use, a highly effective method of contraception
• Are willing and able to comply with all aspects of the protocol
• Provide written informed consent

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• Any subject that has a known history of malaria or has traveled to a country with known malarial risk (ie, is designated as "high" or "moderate" risk country according to the list available at http://www.cdc.gov/malaria) within the last year
• Subjects with a history of bowel resection, any malabsorptive disorder, severe gastroparesis, or any gastrointestinal procedure for the purpose of weight loss (including LAP-BANDTM), which would slow gastric emptying and potentially affect PK profiles of E2006
• Subjects with a known history of clinically significant drug or food allergies
• Subjects who experienced a weight loss or gain of greater than 10% between Screening and prior to dosing
• Subjects who had a clinically significant illness that required medical treatment within 8 weeks or a clinically significant infection within 4 weeks of dosing
• Subjects with any clinically abnormal symptom or organ impairment found in medical history, symptoms or signs, vital sign measurements, electrocardiogram (ECG) findings, or laboratory test results that require medical treatment found in medical history or at screening and baseline
• Subjects known to be positive for human immunodeficiency virus, or subjects who have positive hepatitis B or hepatitis C screening test results
• Subjects who have a history of drug or alcohol dependency or abuse (as defined by The Diagnostic and Statistical Manual of Mental Disorders V criteria) within approximately 2 years prior to Screening, or who have a positive urine drug test results at Screening or Baseline
• Subjects who received blood products within 4 weeks, donated blood within 8 weeks, or donated plasma within 1 week of dosing
• Subjects who used hormonal replacement therapy within 3 months prior to dosing
• Subjects who used any drugs, over-the-counter (OTC) medications, nutritional supplements (eg, products containing St John's wort), excessive doses of vitamins (in the opinion of the principal investigator), herbal preparations, or foods or beverages known to modulate CYP (eg, CYP3A4) or transporters within 4 weeks prior to dosing, or who are unwilling to abstain from using these during the study
• Subjects who engaged in intense physical activity within 1 week prior to Baseline (eg, weight training)
• Subjects who smoke or have used tobacco or nicotine-containing products within 3 months prior to dosing
• Subjects who habitually consume more than 400-mg caffeine per day

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

PPD Development LLC

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

Rifampin; Itraconazole; Midazolam; Bupropion

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Piperazines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Propiophenones; Ketones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2014
• First Posted: March 13, 2014
• Study Start: February 1, 2014
• Primary Completion: April 1, 2014
• Study Completion: June 1, 2014
• Last Updated: November 3, 2015

Record last verified: 2015-11

Locations

US (1)