NCT00245986

Effect of Genetics on Metabolism of Efavirenz

Completed Phase 4 Last updated 2 July 2017

What this trial tests

Phase 4 trial testing Blood draw in Metabolism in 350 participants. Completed in 20 May 2008.

Timeline

18 October 2005

20 May 2008

Quick facts

Lead sponsor	National Institutes of Health Clinical Center (CC)
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Primary purpose	treatment
Enrollment	350
Start date	18 October 2005
Estimated completion	20 May 2008
Sites	1 location across United States

Drugs / interventions tested

• Blood draw — full drug profile →

Conditions studied

• Metabolism — all drugs for Metabolism →

Sponsor

National Institutes of Health Clinical Center (CC)

Who can join

Adults 18 to 55, any sex, with Metabolism. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study will evaluate the effects of genetics on metabolism of the anti-HIV medicine efavirenz (Sustiva) and will see if Efavirenz interacts with bupropion (Zyban or Wellbutrin), a drug commonly used to treat depression and to help people quit smoking. Efavirenz is metabolized by an enzyme called CYP2B6, which is thought to be more active in some people than in others, depending on their genetic makeup. The rate of metabolism of the drug can affect how the body responds it and perhaps the ability of the HIV virus to develop resistance to it.

Healthy volunteers between 18 and 55 years of age who are non-smokers and HIV-infected men and women 18 years of age and older who are taking efavirenz along with two or three nucleoside reverse transcriptase inhibitors may be eligible for this study. Candidates are screened with a medical history and physical examination and blood tests, including tests to determine which genes they have for four different proteins or enzymes (CYP2B6, CYP3A4, CYP3A5, and MDR1) that metabolize drugs.

Participants are assigned to one of three groups for the following procedures:

-HIV-infected individuals: Blood samples are drawn to measure efavirenz levels, as follows: On the last day of taking efavirenz, the subject skips his or her usual evening efavirenz dose the night before sampling. The next morning at clinic, a catheter (flexible plastic tube) is inserted into a vein in the subject's arm for collecting blood samples. After the first sample is drawn, the subject takes a dose of efavirenz. Eight more blood samples are collected at 1, 2, 4, 6, 8, 12, 24 and 48 hours after taking the efavirenz tablet. (The catheter is removed after the 12-hour sample and the subject is discharged home, and then returns to the clinic for the 24- and 48-hour samples, which are collected through a needle inserted into an arm vein.) The subject returns to the clinic four more times for a single blood draw at 7, 14, 21 and 28 days after stopping efavirenz.

HIV-infected patients whose HIV viral load reaches 1,000 copies/L or more within 12 months after completing the study are asked to return to the clinic for a blood draw to check the genotype of the virus for drug resistance.

* Healthy Volunteers - Group 1: Blood samples are drawn to measure efavirenz levels, as follows: Participants take one efavirenz tablet once a day for 13 to 15 days. On the last day of taking efavirenz, the subject takes his/her last dose of efavirenz in clinic, where blood is then collected as described above for HIV-infected individuals.
* Healthy Volunteers - Group 2: A catheter is inserted into a vein in the subject's arm and a blood sample is drawn through the catheter. The subject then takes a single bupropion tablet and additional blood samples are drawn at 1,2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 and 48 hours after the dose to measure the amount of drug in the blood. Subjects begin taking efavirenz 0 to 6 days after the last bupropion blood level is measured. As above, subjects will take one efavirenz tablet once a day for 13 to 15 days. On the last day of taking efavirenz, a catheter is inserted into the subject's arm. Two blood samples are drawn through the catheter, the subject takes the daily dose of efavirenz along with a bupropion tablet. Eleven additional blood samples are drawn at 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours after taking the pills to measure blood levels of bupropion. Eight additional samples are collected at 1, 2, 4, 6, 8, 12, 24, and 48 hours to measure efavirenz blood levels. (The catheter is removed after the 12-hour sample and the subject is discharged home; the 24- and 48-hour samples are collected through a needle inserted into an arm vein.)

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.