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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005762
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : July 22, 2013
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Indinavir sulfate Drug: Ritonavir Drug: Amprenavir Drug: Nelfinavir mesylate Drug: Efavirenz Drug: Saquinavir Not Applicable

Detailed Description:

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 Type : Interventional  (Clinical Trial)
Enrollment : 90 participants
Primary Purpose: Treatment
Official Title: Pharmacokinetic Interaction Studies of Amprenavir (APV), Efavirenz (EFV), and a Second Protease Inhibitor in HIV-Seronegative Volunteers
Study Start Date : March 2001
Actual Study Completion Date : May 2004

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria

Volunteers may be eligible for this trial if they:

  • Are HIV negative.
  • Are 18 to 65 years old.
  • Agree to practice birth control and not donate sperm while on the study and for 3 months after, if a man. (This study has been changed. Male volunteers are now prohibited from donating sperm.)
  • Have a stable weight during the past 6 months of at least 110 pounds and are close to ideal body weight.

Exclusion Criteria

Volunteers will not be eligible for this trial if they:

  • Are women able to have children.
  • Have heart or blood disease, kidney disease, stomach or intestinal problems, conditions affecting the nervous system, hormonal problems, any immune system problems, lung disease, or mental conditions, including the following: high blood pressure, heart disease, diabetes, asthma, elevated cholesterol, elevated triglycerides, inflamed pancreas, and blood-clotting disorders requiring anticoagulation.
  • Have any stomach or intestinal problem that may interfere with the ability to take drugs
  • Have any other medical condition that may interfere with being part of the study.
  • Have been diagnosed with serious mental disorders such as depression, bipolar affective disorder, schizophrenia, or attempted suicide. Patients who have had less serious mental conditions that have been resolved may be included in the study, with approval.
  • Have received protease inhibitors, nonnucleoside reverse transcriptase inhibitors, or experimental agents (not approved by the FDA for the use for which it is being tested) within 60 days of study entry.
  • Have received treatment for an infection or other medical illness within 14 days of study entry.
  • Have had high unexplained fever, or an illness with high fever lasting 3 or more days within 14 days of study entry.
  • Have a history of allergies to any of the study drugs or their components, such as gelatin.
  • Have used prescribed medications within 14 days of study entry.
  • Have used natural or homeopathic remedies including herbal teas within 14 days of entering the study.
  • Are unable to follow the schedule for study drugs during the trial.
  • Are unable to participate in the blood level studies.
  • Actively abuse drugs or alcohol.
  • Change existing tobacco smoking habits during the study.
  • Cannot avoid strenuous exercise or constant activity for the study period.
  • Cannot avoid taking caffeine or alcohol at certain times before the blood level studies.
  • Have had an allergic reaction to any drugs.
  • (This protocol has been changed. Entry criteria are different from the original.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005762

United States, California
Stanford CRS
Palo Alto, California, United States, 943055107
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 462025250
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States
United States, Ohio
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Tennessee
Vanderbilt Univ. Med. Ctr., AIDS Clinical Trials Ctr.
Nashville, Tennessee, United States, 37203
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Gene Morse

Publications of Results:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00005762     History of Changes
Other Study ID Numbers: A5043
10671 ( Registry Identifier: DAIDS ES )
ACTG A5043
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: July 22, 2013
Last Verified: July 2013

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Interactions
Drug Therapy, Combination
HIV Protease Inhibitors
Dosage Forms
VX 478
Anti-HIV Agents

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers