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Healthy SubjectsPhase 1NCT02085967

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

A Phase 1 study testing rifampin 600 mg, itraconazole 200 mg and midazolam 2 mg with bupropion 75 mg in people with Healthy Subjects, run by Eisai Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Subjects
What is being tested?
rifampin 600 mg, itraconazole 200 mg and midazolam 2 mg with bupropion 75 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
106 participants
Where
1 siteUnited States
Study dates
Feb 2014to Jun 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 22Show fewer
  • 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
  • Subjects who participated (received investigational product) in another clinical trial less than 1 month (or 5 elimination half-lives of the investigational product) prior to dosing or who are currently enrolled in another clinical trial
  • Subjects with a disease that may influence the outcome of the study, such as psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or subjects who have a congenital abnormality in metabolism, or subjects who have any condition that would make him or her, in the opinion of the investigator, unsuitable for the study or who, in the opinion of the investigator, are not likely to complete the study for any reason
  • Restrictions on concomitant medications, food and beverages:
  • Prescription drugs are prohibited within 4 weeks of dosing and OTC medications within 2 weeks prior to dosing and until the Termination Visit
  • Smoking or use of tobacco or nicotine-containing products is prohibited within 4 weeks prior to dosing and until Termination Visit
  • Intake of caffeinated beverages or food is prohibited 72 hours prior to dosing and throughout the entire study
  • Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug metabolizing enzymes and transporters (eg, alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats) is prohibited within 2 weeks prior to dosing until the Termination Visit

Trial locations and contacts

1 site in 1 country.

United States1 site

  • PPD Development LLC

    Austin, Texas, 78744

Other trials in United States

About this study

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.

Being tested
rifampin 600 mg, itraconazole 200 mg, midazolam 2 mg with bupropion 75 mg, E2006
Keywords
Healthy, Metabolism, Drug-Drug Interactions

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rifampin 600 mgDrug

  • itraconazole 200 mgDrug

  • midazolam 2 mg with bupropion 75 mgDrug

  • E2006Drug

Study groups in NCT02085967
Study groupRoleWhat they receive
E2006 Part AExperimentalE2006 10-mg tablets alone and in combination with rifampin 600 mg or itraconazole 200 mg
Receives: Drug: rifampin 600 mg; Drug: itraconazole 200 mg; Drug: E2006
E2006 Part BExperimentalE2006 10-mg tablets alone and in combination with midazolam 2 mg plus bupropion 75 mg
Receives: Drug: midazolam 2 mg with bupropion 75 mg; Drug: E2006

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

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

  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): Cmax

    Maximum observed concentration

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

Secondary outcomes (7)

  1. 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

    Time at which the highest drug concentration occurs

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

  2. Pharmacokinetics of E2006: AUC(0-8h)

    Area under the concentration-time curve from time zero time to 8 hours after dosing (E2006 only)

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

  3. Pharmacokinetics of E2006: AUC(0-24h)

    Area under the concentration-time curve from time zero time to 24 hours after dosing (E2006 only)

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

  4. 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)

    Area under the concentration-time curve from zero time to time 72 hours after dosing

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

  5. 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

    Terminal elimination phase half-life

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

  6. 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

    Apparent total clearance after extravascular administration

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

  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): AUC(0-inf), metabolite ratio

    Ratio of S,S-hydroxybupropion to S-buproprion

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completionApr 2014
  4. Study completionJun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
106 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02085967
Sponsor's protocol ID
E2006-A001-004
Status last verified
Nov 2015
First submitted
10 Mar 2014
Last updated
3 Nov 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rifampin 600 mg, itraconazole 200 mg and midazolam 2 mg with bupropion 75 mg in people with Healthy Subjects, run by Eisai Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02085967.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2015.

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