Drug Interactions of Amprenavir and Efavirenz, in Combination With a Second Protease Inhibitor, in HIV-Negative Volunteers

2014-08-27 03:57:39 | BioPortfolio


The purpose of this study is to measure the blood levels of amprenavir (APV) alone, APV combined with efavirenz (EFV), and APV/EFV combined with a third drug (nelfinavir [NFV], indinavir [IDV], ritonavir soft gel capsules [RTV sgc], or saquinavir soft gel capsules [SQV sgc]).

Anti-HIV therapy with 3 or 4 drugs is currently the recommended approach for treating HIV infections. Doctors need to know the best dosages of certain drugs when they are given in combination. This study will measure the blood levels of APV alone, APV combined with EFV, and APV/EFV plus a second PI in healthy volunteers. It will study the safety and tolerance of these drugs.


Triple-drug antiretroviral regimens have become the recommended approach to therapy for HIV infection. [AS PER AMENDMENT 12/4/00: The clinical use of multiple-drug antiretroviral regimens containing various combinations of nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has become a widespread approach to therapy for HIV infection, especially for patients previously treated with PIs.] Since the introduction of PIs, a greater awareness of the relationship between optimal suppression of viral replication, genotypic resistance, and viral rebound has led to the design of more potent antiretroviral drug combinations. Two ACTG clinical trials addressing the issue of virologic failure utilize antiviral regimens that include 2 NRTIs, 2 PIs (one of which is APV), and EFV (NNRTI). Although this drug combination is logical, there is limited PK data to guide the dosing selection. This study enrolls healthy volunteers to obtain PK profiles and metabolic assessments of APV/EFV before and after the addition of a second PI [AS PER AMENDMENT 12/4/00: APV alone, APV combined with EFV, and APV/EFV combined with a second PI].

Upon study entry, volunteers receive APV plus EFV for 2 weeks. [AS PER AMENDMENT 12/4/00: Volunteers receive a single dose of APV alone on Day 0, EFV alone on Days 1 to 10, and APV combined with EFV on Days 11 to 13.] After 2 weeks [AS PER AMENDMENT 12/4/00: After completion of the second PK visit], volunteers are randomized to 1 of 5 treatment arms to add a second PI to the APV/EFV drug combination for 2 more weeks [AS PER AMENDMENT 12/4/00: for at least 1 week]. The treatment arms are as follows:

Arm A (control arm): APV and EFV alone. Arm B: APV and EFV plus IDV [AS PER AMENDMENT 12/4/00: APV and EFV plus NFV]. Arm C: APV and EFV plus NFV [AS PER AMENDMENT 12/4/00: APV and EFV plus IDV]. Arm D: APV and EFV plus RTV sgc. Arm E: APV and EFV plus SQV sgc. On Day 14, 15, or 16, volunteers return to the clinic for PK testing following the dual-drug regimen, and again on Day 29, 30, or 31 following the triple-drug regimen (or continued dual-drug regimen for Arm A). [AS PER AMENDMENT 12/4/00: Volunteers attend clinics for PK testing on Days 0 and 1 (first visit), after taking the dual-drug regimen for at least 3 days (second visit, e.g., on Day 14 or after), and after taking the triple-drug regimen (or, if in Arm A, after continuing on the dual-drug regimen) for at least 7 days (third visit).] Before each PK testing, volunteers complete an Adherence Questionnaire. [AS PER AMENDMENT 12/4/00: The Adherence Questionnaire is administered at the second and third PK visits.] Volunteers maintain a food diary. Two to three weeks after completing the drug regimen [AS PER AMENDMENT 12/4/00: Within 2-3 weeks after the third PK visit], volunteers return to the clinic for evaluations and urine and blood sampling.

Study Design

Control: Dose Comparison, Endpoint Classification: Pharmacokinetics Study, Primary Purpose: Treatment


HIV Infections


Indinavir sulfate, Ritonavir, Amprenavir, Nelfinavir mesylate, Efavirenz, Saquinavir


Univ of Southern California / LA County USC Med Ctr
Los Angeles
United States




National Institute of Allergy and Infectious Diseases (NIAID)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:57:39-0400

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Medical and Biotech [MESH] Definitions

Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.

An enzyme that catalyzes the activation of sulfate ions by ATP to form adenosine-5'-phosphosulfate and pyrophosphate. This reaction constitutes the first enzymatic step in sulfate utilization following the uptake of sulfate. EC

An arylsulfatase that catalyzes the hydrolysis of the 4-sulfate groups of the N-acetyl-D-galactosamine 4-sulfate units of chondroitin sulfate and dermatan sulfate. A deficiency of this enzyme is responsible for the inherited lysosomal disease, Maroteaux-Lamy syndrome (MUCOPOLYSACCHARIDOSIS VI). EC

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