Efavirenz, Metabolism and Pharmacokinetics ChangesNCT01104376
Determine the Effects of Gene Differences and Voriconazole on Enzyme CYP2B6 Activity in the Liver in Healthy Volunteers
A study testing Efavirenz and voriconazole in people with Efavirenz, Metabolism and Pharmacokinetics Changes, run by Indiana University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Efavirenz, Metabolism and Pharmacokinetics Changes
- What is being tested?
- Efavirenz and voriconazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Apr 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- Efavirenz, voriconazole
- Keywords
- Cytochrome P450, CYP2B6, Voriconazole, Efavirenz, Pharmacokinetics, Drug-Interactions, Pharmacogenetics, Healthy volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EfavirenzDrug
Also called Sustiva
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.
voriconazoleDrug
Also called Vfend
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Efavirenz; Drug: voriconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24h after efavirenz
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2010 (estimated)
- Study startMar 2010
- Primary completionApr 2011
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Efavirenz, Metabolism and Pharmacokinetics ChangesStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Zeruesenay Desta, Indiana University
- Investigators
- Zeruesenay Desta, PhD, Principal investigator, IU Department of Medicine/Division of Clinical Pharmacology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01104376
- Sponsor's protocol ID
- 0808-16
- Other IDs
- R01GM078501
- Status last verified
- Dec 2014
- First submitted
- 12 Apr 2010
- Last updated
- 17 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27600044
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Cytochrome P450 2B6 Genetic Polymorphism and Voriconazole on CYP2B6 Activity in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01104376
- Acronym / sponsor ID
- 0808-16
- Keywords
- Cytochrome P450, CYP2B6, Voriconazole, Efavirenz, Pharmacokinetics, Drug-Interactions, Pharmacogenetics, Healthy volunteers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS)
- Study start
- Mar 2010
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 15 Apr 2010 (estimated)
- Results
- Posted 17 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CYP2B6 | Experimental | Drug: Efavirenz, Drug: voriconazoleHealthy 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EfavirenzAlso: SustivaIn 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 | CYP2B6 |
| voriconazoleAlso: VfendIn 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 | CYP2B6 |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27600044Desta 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zeruesenay Desta, PhD principal investigator
IU Department of Medicine/Division of Clinical Pharmacology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Efavirenz and voriconazole in people with Efavirenz, Metabolism and Pharmacokinetics Changes, run by Indiana University 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 5 inclusion and 16 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 17 Dec 2014. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
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). 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 NCT01104376, which also lists 1 linked publication.
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 17 Dec 2014.