Determine the Effects of Gene Differences and Voriconazole on Enzyme CYP2B6 Activity in the Liver in Healthy Volunteers

December 16, 2014 updated by: Zeruesenay Desta, Indiana University

Effect of Cytochrome P450 2B6 Genetic Polymorphism and Voriconazole on CYP2B6 Activity in Healthy Volunteers

The purpose of this study is to see if administration of medicines and genetic differences affects the activity of a liver enzyme called CYP2B6 in healthy volunteers.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators will test the hypothesis that CYP2B6 genetic variants that show effects in vitro also influence the in vivo activity of CYP2B6 and its responsiveness to metabolic inhibition, using the metabolism of efavirenz (100 mg dose) as a marker of activity. The metabolism and pharmacokinetics of efavirenz will be determined in a total of 60 healthy volunteers with CYP2B6*1/*1, CYP2B6*1*6 and CYP2B6*6*6 at baseline (control) and after pretreatment with voriconazole.

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female subject between 18 and 55 years of age.
  • Healthy individuals without any significant medical conditions as determined by a screening performed at University.
  • Adherence to the study dietary and medication restrictions.
  • Willingness to refrain from smoking or use of tobacco or marijuana one week before the start of the study and until completion of the study which will be a total of 17 days.
  • Ability to commit the time requested for this study.

Exclusion Criteria:

  • Underweight (weighs less than 50kg or 110lb) or over weight [body mass index (BMI) greater than 32].
  • Drug or alcohol abuse (more than 3 alcoholic drinks per day on a regular basis).
  • History of intolerance or allergic reaction (e.g. rash) to efavirenz and/or voriconazole.
  • Significant health conditions such heart, gastrointestinal disorders, liver, or kidney diseases that may be exacerbated during the course of the study.
  • History or current psychiatric illness (e.g. depression, anxiety, or nervousness).
  • History or current eye sight disturbances (e.g. blurred vision).
  • Serious infection within the last 2 weeks.
  • Blood donation within the past two months.
  • Screening results that do not fall in a healthy range.
  • Regularly taking prescriptions (except hormonal agents, e.g. oral contraceptives), over-the-counter, herbal or dietary supplements, and alternative medications and are unable or unwilling to stop taking them one week before and during the study periods.
  • Female with a positive pregnancy test.
  • Female breastfeeding.
  • Females of child-bearing potential who are unable or unwilling to either practice abstinence or use appropriate birth control up until the study completion, which will take a total of 17 days.
  • Participation in a research study involving intensive blood sampling and/or have use study drugs in the last two months.
  • Employed or student under supervision of any of the investigators of this study.
  • Inability to state a good understanding of this study including risks and requirements, and inability to follow the rules of this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CYP2B6

Healthy volunteers will receive Efavirenz and Vericonazole as follow:

In phase 1 day 1 (control phase) a single 100mg dose of efavirenz will be administered. In phase 2 (voriconazole pretreatment phase), the subject will be pretreated with voriconazole (400mg twice daily on phase 2 day 8 and then 200mg twice daily for the next consecutive 8 days. In phase 3 (efavirenz plus voriconazole phase), the subject will receive on phase 3 day 10 100mg single dose of efavirenz along with 200mg of voriconazole twice daily.
Drug: Efavirenz

In phase 1 day 1 (control phase) a single 100mg dose of efavirenz will be administered.

In phase 2 (voriconazole pretreatment phase), the subject will be pretreated with voriconazole (400mg twice daily on phase 2 day 8 and then 200mg twice daily for the next consecutive 8 days. In phase 3 (efavirenz plus voriconazole phase), the subject will receive on phase 3 day 10 100mg single dose of efavirenz along with 200mg of voriconazole twice daily.

Other Names:
  • Sustiva
Drug: voriconazole

In phase 1 day 1 (control phase) a single 100mg dose of efavirenz will be administered.

In phase 2 (voriconazole pretreatment phase), the subject will be pretreated with voriconazole (400mg twice daily on phase 2 day 8 and then 200mg twice daily for the next consecutive 8 days. In phase 3 (efavirenz plus voriconazole phase), the subject will receive on phase 3 day 10 100mg single dose of efavirenz along with 200mg of voriconazole twice daily.

Other Names:
  • Vfend

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure Efavirenz Clearance
Time Frame: Baseline, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24h after efavirenz
Effect of steady-state voriconazole on efavirenz Clearance in healthy volunteers (n=61) administered a single 100 mg oral dose of efavirenz at baseline (control phase) and after treatment with voriconazole to steady-state.
Baseline, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24h after efavirenz

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Collaborators

National Institutes of Health (NIH)
National Institute of General Medical Sciences (NIGMS)

Investigators

  • Principal Investigator: Zeruesenay Desta, PhD, IU Department of Medicine/Division of Clinical Pharmacology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

April 12, 2010

First Submitted That Met QC Criteria

April 14, 2010

First Posted (Estimate)

April 15, 2010

Study Record Updates

Last Update Posted (Estimate)

December 17, 2014

Last Update Submitted That Met QC Criteria

December 16, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0808-16
  • R01GM078501 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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