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| Sponsor: | National Institute of Allergy and Infectious Diseases (NIAID) |
|---|---|
| Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00000877 |
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 I |
| Study Type: | Interventional |
| Study Design: | Treatment, Parallel Assignment, Safety Study |
| Official Title: | Steady-State Pharmacokinetic Interaction Study of Indinavir and Rifabutin |
| Estimated Enrollment: | 31 |
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 |
Inclusion Criteria
You may be eligible for this study if you:
Exclusion Criteria
You will not be eligible for this study if you:
Contacts and 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 | |
| Study Chair: | Charles Flexner | |
| Study Chair: | Constance Benson | |
| Study Chair: | Judith Currier |
More Information
| Study ID Numbers: | ACTG 365 |
| Study First Received: | November 2, 1999 |
| Last Updated: | August 5, 2008 |
| ClinicalTrials.gov Identifier: | NCT00000877 History of Changes |
| Health Authority: | United States: Federal Government |
|
Rifabutin Drug Therapy, Combination HIV Protease Inhibitors |
Indinavir HIV Seronegativity Anti-HIV Agents |
|
Anti-Infective Agents Sexually Transmitted Diseases, Viral Rifabutin Slow Virus Diseases Indinavir Molecular Mechanisms of Pharmacological Action Infection Anti-Bacterial Agents Anti-Retroviral Agents Therapeutic Uses Retroviridae Infections RNA Virus Infections HIV Protease Inhibitors Anti-HIV Agents |
Immune System Diseases Acquired Immunodeficiency Syndrome Enzyme Inhibitors Antiviral Agents Immunologic Deficiency Syndromes Pharmacologic Actions Antibiotics, Antitubercular Protease Inhibitors Virus Diseases HIV Infections Sexually Transmitted Diseases Lentivirus Infections Antitubercular Agents |