A Study on Possible Interactions Between Protease Inhibitors (Anti-HIV Drugs) and Drugs Which Lower the Level of Fat in Your Blood

NCT ID: NCT00000941

Last Updated: 2021-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2002-03-31

Brief Summary

The purpose of this study is to find out whether taking protease inhibitors (anti-HIV drugs) together with lipid-lowering drugs (drugs which lower the amount of fat in the blood) has an effect on the level of drugs found in the blood compared to when these drugs are taken separately. The three protease inhibitors given in this study are ritonavir, saquinavir, and nelfinavir. The lipid-lowering drugs given are pravastatin, simvastatin, and atorvastatin.

Anti-HIV drug therapy using protease inhibitors has become very common treatment for HIV-positive patients. Recently, however, serious side effects involving how the body uses fat have been reported in people taking protease inhibitors. Examples of these side effects are redistribution of body fat and development of diabetes. People taking protease inhibitors have been found to have higher levels of fat in their blood than is normal, which can cause heart problems. It is hoped that giving lipid-lowering drugs can help prevent serious heart problems. First, however, it is important to see what happens when protease inhibitors and lipid-lowering drugs are given together.

Detailed Description

Potent antiretroviral therapy has become the standard of care for persons with HIV infection and AIDS. Recently, however, a number of complications have emerged with the widespread use of protease inhibitor (PI)-based regimens, including: hyperlipidemia, hypertriglyceridemia, diabetes mellitus, and lipodystrophy. Concern over the possibility of premature myocardial infarction has led health care providers and patients to consider treating these lipid metabolism disorders. Statin compounds have beneficial effects as lipid-lowering agents, and thereby reduce the risk of cardiovascular complications. Statin compounds such as pravastatin, simvastatin, and atorvastatin are increasingly being prescribed in persons taking PI-based potent antiretroviral therapy. It is important to determine whether there are significant drug-drug interactions between the statin compounds and PIs.

Fourteen healthy participants for each cohort of Arm A are stabilized on a fixed regimen of pravastatin (Arm A1), simvastatin (Arm A2), or atorvastatin (Arm A3) for 4 days. A baseline pharmacokinetic (PK) evaluation is completed on Day 4. Pravastatin (or simvastatin or atorvastatin) dosing stops following the Day 4 dose and PK evaluation. On Day 5, a ritonavir and saquinavir combination regimen is initiated and continued through Day 18 of the study. Pravastatin (or simvastatin or atorvastatin) dosing resumes on Day 15 and continues through Day 18. A repeat PK evaluation of pravastatin (or simvastatin or atorvastatin) in the context of combination therapy is carried out on Day 18.

Fourteen healthy participants are assigned to Arm B; these participants begin a 2-week regimen of nelfinavir. On Day 14, a baseline PK profile of nelfinavir and its M8 metabolite is carried out. Pravastatin is then added to the regimen for Days 15 to 18. On Day 18, a repeat PK evaluation of nelfinavir and the M8 metabolite is carried out in the context of combination therapy.

Conditions

HIV Infections

Keywords

Drug Interactions; HIV Protease Inhibitors; Ritonavir; HIV Seronegativity; Saquinavir; Nelfinavir; Anticholesteremic Agents

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Pravastatin sodium

Intervention Type: DRUG

Simvastatin

Intervention Type: DRUG

Atorvastatin calcium

Intervention Type: DRUG

Ritonavir

Intervention Type: DRUG

Nelfinavir mesylate

Intervention Type: DRUG

Saquinavir

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

You may be eligible for this study if you:

• Are HIV-negative.
• Are between the ages of 18 and 60.
• Agree to use a barrier method of birth control (e.g., a condom) during the study.

Exclusion Criteria

You will not be eligible for this study if you:

• Have a history of a chronic illness such as high blood pressure, heart disease, arthritis, or diabetes.
• Are pregnant or breast-feeding.
• Are taking certain medications.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesca Aweeka

Role: STUDY_CHAIR

Carl Fitchenbaum

Role: STUDY_CHAIR

Locations

Univ of Southern California / LA County USC Med Ctr

Los Angeles, California, United States

San Francisco Gen Hosp

San Francisco, California, United States

Stanford Univ Med Ctr

Stanford, California, United States

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States

Univ of Miami School of Medicine

Miami, Florida, United States

Univ of Hawaii

Honolulu, Hawaii, United States

Indiana Univ Hosp

Indianapolis, Indiana, United States

Tulane Univ School of Medicine

New Orleans, Louisiana, United States

Johns Hopkins Hosp

Baltimore, Maryland, United States

Univ of Minnesota

Minneapolis, Minnesota, United States

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Julio Arroyo

West Columbia, South Carolina, United States

Univ of Washington

Seattle, Washington, United States

Countries

United States

References

Fichtenbaum CJ, Gerber JG, Rosenkranz SL, Segal Y, Aberg JA, Blaschke T, Alston B, Fang F, Kosel B, Aweeka F; NIAID AIDS Clinical Trials Group. Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS. 2002 Mar 8;16(4):569-77. doi: 10.1097/00002030-200203080-00008.

Reference Type: BACKGROUND

PMID: 11873000 (View on PubMed)

Wanke C. Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047, by Fichtenbaum et al. AIDS. 2003;17 Suppl 4:S109-10. No abstract available.

Reference Type: BACKGROUND

PMID: 15080191 (View on PubMed)

Other Identifiers

10891

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5047

Identifier Type: -

Identifier Source: secondary_id

A5047

Identifier Type: -

Identifier Source: org_study_id