Clinical trial NCT00000941: A Study on Possible Interactions Between Protease Inhibitors (Anti-HIV Drugs) and Drugs Which Lower the Level of Fat in Your Blood
Official title: Evaluation of Potential Pharmacokinetic Interactions Between Protease Inhibitors and Lipid Lowering Agents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Drug Interactions
HIV Protease Inhibitors
Ritonavir
HIV Seronegativity
Saquinavir
Nelfinavir
Anticholesteremic Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: New Orleans
country: United States
facility: Tulane Univ School of Medicine
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
Study officials:
name: Francesca Aweeka
role: STUDY_CHAIR
name: Carl Fitchenbaum
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.