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

November 2, 1999
May 17, 2012
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Complete list of historical versions of study NCT00000941 on ClinicalTrials.gov Archive Site
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A Study on Possible Interactions Between Protease Inhibitors (Anti-HIV Drugs) and Drugs Which Lower the Level of Fat in Your Blood
Evaluation of Potential Pharmacokinetic Interactions Between Protease Inhibitors and Lipid Lowering Agents

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.

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.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Pravastatin sodium
  • Drug: Simvastatin
  • Drug: Atorvastatin calcium
  • Drug: Ritonavir
  • Drug: Nelfinavir mesylate
  • Drug: Saquinavir
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
56
March 2002
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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.
Both
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000941
A5047, 10891, ACTG A5047
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: Francesca Aweeka
Study Chair: Carl Fitchenbaum
National Institute of Allergy and Infectious Diseases (NIAID)
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP