Study of How Indinavir (an Anti-HIV Drug) and Rifabutin (a Drug Used to Treat MAC, an HIV-Associated Disease) Interact in HIV-Positive and HIV-Negative Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000877
First received: November 2, 1999
Last updated: May 21, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to evaluate the safety of giving indinavir and rifabutin at the same time (simultaneously) vs 4 hours apart (staggered) to HIV-positive and HIV-negative adults.

It is important to determine which medications for HIV-associated diseases, such as Mycobacterium avium complex (MAC) disease, can be given safely and effectively with anti-HIV drugs. Indinavir and rifabutin have been given simultaneously in the past with good results. This study seeks to examine if staggering the doses will make the 2 drugs more effective. HIV-negative volunteers are used in this study to examine the effect of rifabutin on indinavir and the effect of staggered rifabutin doses. The effect of rifabutin on the drug activity of indinavir is evaluated in HIV-positive patients.


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Rifabutin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Steady-State Pharmacokinetic Interaction Study of Indinavir and Rifabutin

Resource links provided by NLM:


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

Estimated Enrollment: 31
Study Completion Date: October 2000
Detailed Description:

Currently, rifabutin is the only rifamycin that can be administered with indinavir. ACTG 365 is the first formal study of the pharmacokinetics of this dosing combination regimen in HIV seropositive patients. It is hypothesized that staggered administration of rifabutin and indinavir might minimize their pharmacokinetic interaction. If the intestinal tract plays a significant role in the presystemic clearance of rifabutin, the inhibitory activity of indinavir on rifabutin could depend on either luminal concentrations of indinavir, systematic concentrations of indinavir, or both. If luminal concentrations are important, then the interaction between these 2 drugs will be maximal when administered simultaneously, and minimal when their oral administration is staggered. Finally, since indinavir has a half-life of 1.8 hours, its effects on rifabutin's systematic clearance may be much less when administration of these drugs is staggered by 4 hours as compared with simultaneous administration with rifabutin. If the interaction on rifabutin is minimized, then the rifabutin levels may be suboptimal for treatment of tuberculosis in patients who are not administered the 2 drugs simultaneously. It is, therefore, important to define the magnitude of the effect of staggered vs simultaneous drug administration in order to clarify dose and regimen recommendations in HIV-infected patients with tuberculosis who also require protease inhibitor therapy.

Study Arm A is a multiple-dose, 3-period, sequential study in 18 evaluable HIV-infected indinavir-naive male and female volunteers [AS PER AMENDMENT 11/16/98: Arm A will be assessed in 18 evaluable HIV-seronegative patients]. Patients receive 3 different treatments consisting of 14 days of administration: rifabutin alone (Period IA); indinavir plus rifabutin (Period IIA); and indinavir plus rifabutin (Period IIIA). Study Arm B is a multiple-dose, 2-period, sequential study in 10 evaluable HIV-infected male and female volunteers. Patients receive 2 different treatments, each consisting of 14 days of administration; indinavir alone (Period IB); and indinavir plus rifabutin (Period IIB). Patients on both arms take each dose of their study medications with water. [AS PER AMENDMENT 8/8/97: Patients treated on Arm A are randomized, following Period IA therapy, to Period IIA or IIIA therapy for 14 days, then are crossed over to the alternate regimen for 14 days.] [AS PER AMENDMENT 4/17/98: After completion of therapy on Arm A or B, patients continue therapy with indinavir alone for 7 days.] [AS PER AMENDMENT 11/16/98: The final 7 days of indinavir dosing has been eliminated for patients on Arm A. Also per this amendment, to ensure compliance, Arm A patients' rifabutin supply will be dispensed in containers fitted with an electronic monitoring cap device.]

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

You may be eligible for this study if you:

  • Are HIV-positive or HIV-negative.
  • Agree to practice abstinence or to use birth control during the study.

Exclusion Criteria

You will not be eligible for this study if you:

  • Have an active opportunistic (HIV-associated) disease or other disease requiring medication within 14 days of study entry.
  • Have a history of illness that might put you at risk if given either of the study drugs.
  • Have had any severe allergies to any substance in the past.
  • Have a history of kidney stones.
  • Have a medical condition, or problems with use of alcohol or drugs, which would keep you from completing the study.
  • Have had tuberculosis and have never been treated for it.
  • 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: NCT00000877

Locations
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Univ of Southern California / LA County USC Med Cntr
Los Angeles, California, United States, 90033
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, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, New York
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Cornell Univ Med Ctr
New York, New York, United States, 10021
Sponsors and Collaborators
Investigators
Study Chair: Charles Flexner
Study Chair: Constance Benson
Study Chair: Judith Currier
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000877     History of Changes
Other Study ID Numbers: ACTG 365, 11328
Study First Received: November 2, 1999
Last Updated: May 21, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Rifabutin
Drug Therapy, Combination
HIV Protease Inhibitors
Indinavir
HIV Seronegativity
Anti-HIV 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
Rifabutin
Indinavir
HIV Protease Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antitubercular
Antitubercular Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on August 26, 2014