- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000877
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
Steady-State Pharmacokinetic Interaction Study of Indinavir and Rifabutin
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.]
Study Type
Enrollment
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90033
- Univ of Southern California / LA County USC Med Cntr
-
Los Angeles, California, United States, 900331079
- Univ of Southern California / LA County USC Med Ctr
-
-
Colorado
-
Denver, Colorado, United States, 80262
- Univ of Colorado Health Sciences Ctr
-
-
Florida
-
Miami, Florida, United States, 331361013
- Univ of Miami School of Medicine
-
-
Indiana
-
Indianapolis, Indiana, United States, 462025250
- Indiana Univ Hosp
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Johns Hopkins Hosp
-
-
New York
-
New York, New York, United States, 10021
- Cornell Univ Med Ctr
-
New York, New York, United States, 10016
- Bellevue Hosp / New York Univ Med Ctr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Interventional Model: Parallel Assignment
Collaborators and Investigators
Investigators
- Study Chair: Charles Flexner
Publications and helpful links
General Publications
- Hamzeh FM, Benson C, Gerber J, Currier J, McCrea J, Deutsch P, Ruan P, Wu H, Lee J, Flexner C; AIDS Clinical Trials Group 365 Study Team. Steady-state pharmacokinetic interaction of modified-dose indinavir and rifabutin. Clin Pharmacol Ther. 2003 Mar;73(3):159-69. doi: 10.1067/mcp.2003.3.
- Hennig S, Svensson EM, Niebecker R, Fourie PB, Weiner MH, Bonora S, Peloquin CA, Gallicano K, Flexner C, Pym A, Vis P, Olliaro PL, McIlleron H, Karlsson MO. Population pharmacokinetic drug-drug interaction pooled analysis of existing data for rifabutin and HIV PIs. J Antimicrob Chemother. 2016 May;71(5):1330-40. doi: 10.1093/jac/dkv470. Epub 2016 Jan 31.
Study record dates
Study Major Dates
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- Anti-Bacterial Agents
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Antitubercular Agents
- Antibiotics, Antitubercular
- Indinavir
- Rifabutin
Other Study ID Numbers
- ACTG 365
- 11328 (DAIDS ES)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infections
-
University of MinnesotaWithdrawnHIV Infections | HIV/AIDS | Hiv | AIDS | Aids/Hiv Problem | AIDS and InfectionsUnited States
-
University of California, San DiegoUniversity of California, Los Angeles; University of Southern California; California... and other collaboratorsCompleted
-
National Institute of Allergy and Infectious Diseases...Eunice Kennedy Shriver National Institute of Child Health and Human Development...CompletedHIV Infections | HIV SeronegativityUnited States, Puerto Rico
-
Erasmus Medical CenterCompletedHIV/AIDS | Opportunistic Infections, HIV RelatedNetherlands
-
RANDBienestar Human Services, Inc.Completed
-
Ukrainian Institute on Public Health PolicyCompleted
-
University of California, BerkeleyNational Institute of Mental Health (NIMH); Ministry of Health and Social Welfare...Completed
-
Ryerson UniversityCanadian Institutes of Health Research (CIHR); Simon Fraser University; University...Completed
-
University of California, San FranciscoNational Institutes of Health (NIH); ANOVA Health InstituteCompleted
-
McGill UniversityCanadian Institutes of Health Research (CIHR); Université du Québec a MontréalUnknown
Clinical Trials on Indinavir sulfate
-
Merck Sharp & Dohme LLCCompleted
-
Merck Sharp & Dohme LLCCompleted
-
National Institute of Allergy and Infectious Diseases...CompletedHIV InfectionsUnited States
-
Merck Sharp & Dohme LLCCompleted
-
National Institute of Allergy and Infectious Diseases...Withdrawn
-
Merck Sharp & Dohme LLCCompletedHIV InfectionsUnited States
-
Glaxo WellcomeCompleted
-
Glaxo WellcomeCompletedHIV InfectionsUnited States
-
Glaxo WellcomeCompleted
-
National Institute of Allergy and Infectious Diseases...Completed