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

NCT01104376 | Completed Results DMC

• 2 other identifiers: 0808-16R01GM078501
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Efavirenz, Metabolism and Pharmacokinetics Changes

Keywords

Cytochrome P450; CYP2B6; Voriconazole; Efavirenz; Pharmacokinetics; Drug-Interactions; Pharmacogenetics; Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Measure Efavirenz Clearance

  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

Study Arms (1)

CYP2B6

EXPERIMENTAL

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; Drug: voriconazole

Interventions

Efavirenz DRUG

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.

Also known as: Sustiva

CYP2B6

voriconazole DRUG

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.

Also known as: Vfend

CYP2B6

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indiana University: lead
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Related Publications (1)

• Desta Z, Metzger IF, Thong N, Lu JB, Callaghan JT, Skaar TC, Flockhart DA, Galinsky RE. Inhibition of Cytochrome P450 2B6 Activity by Voriconazole Profiled Using Efavirenz Disposition in Healthy Volunteers. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6813-6822. doi: 10.1128/AAC.01000-16. Print 2016 Nov.

  PMID: 27600044 DERIVED

MeSH Terms

Interventions

efavirenz; Voriconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Zeruesenay Desta, PhD
• Organization: Indiana University

zdesta@iupui.edu

317-630-8860

Study Officials

• Zeruesenay Desta, PhD

  IU Department of Medicine/Division of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: April 15, 2010
• Study Start: March 1, 2010
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2013
• Last Updated: December 17, 2014
• Results First Posted: December 17, 2014

Record last verified: 2014-12

Locations

US (1)