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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000941
First received: November 2, 1999
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Pravastatin sodium
Drug: Simvastatin
Drug: Atorvastatin calcium
Drug: Ritonavir
Drug: Nelfinavir mesylate
Drug: Saquinavir
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Potential Pharmacokinetic Interactions Between Protease Inhibitors and Lipid Lowering Agents

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 56
Study Completion Date: March 2002
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000941

Locations
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Hawaii
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Louisiana
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Washington
Univ of Washington
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Francesca Aweeka
Study Chair: Carl Fitchenbaum
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000941     History of Changes
Other Study ID Numbers: A5047, 10891, ACTG A5047
Study First Received: November 2, 1999
Last Updated: May 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Interactions
HIV Protease Inhibitors
Ritonavir
HIV Seronegativity
Saquinavir
Nelfinavir
Anticholesteremic Agents

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Anticholesteremic Agents
Simvastatin
Atorvastatin
Pravastatin
Hypolipidemic Agents
Protease Inhibitors
Saquinavir
Ritonavir
Nelfinavir
HIV Protease Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on August 26, 2014