Tolerance, Safety, and Activity of Rifapentine Alone and in Combination Therapy in AIDS Patients With Mycobacterium Avium Complex Bacteremia.

To determine the antimicrobial activity and tolerability of rifapentine alone and in combination therapy in patients with AIDS and disseminated Mycobacterium avium complex (MAC) bacteremia. To determine the pharmacokinetics of rifapentine and its metabolite, 25-desacetyl, alone and in combination therapy. To determine the pharmacokinetics of azithromycin and clarithromycin (and its 14-OH metabolite) in combination therapy.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Mycobacterium Avium-Intracellulare Infection
• Intervention / Treatment: Drug: Clarithromycin; Drug: Ethambutol hydrochloride; Drug: Azithromycin; Drug: Rifapentine

Detailed Description

This open-label, sequential study is conducted in two parts: a monotherapy phase and a combination treatment phase.

In the monotherapy phase sequential 3-patient cohorts receive 1 of 3 doses of rifapentine monotherapy.

In the combination treatment phase, 12 patients each are randomized to one of three arms:

Arm I: Rifapentine (assigned dose level based on monotherapy phase) plus azithromycin.

Arm II: Rifapentine (assigned dose level) plus clarithromycin. Arm III: Rifapentine (assigned dose level) plus ethambutol.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Hampton Roads Med Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients must have:

• Documented positive HIV serology status.
• Documented AIDS.
• Positive blood culture for MAC from the study-designated microbiology laboratory. NOTE:
• Patients with presumed MAC bacteremia, as evidenced by positive blood, bone marrow, or liver biopsy culture analyzed locally, may be enrolled pending confirmation.
• Minimum of two MAC-associated symptoms, defined as >= grade 1 fever; > grade 1 night sweats, fatigue, diarrhea, abdominal pain, or anorexia; or weight loss > 5% reported within 4 weeks prior to study entry.
• Life expectancy of at least 3 months.

Prior Medication:

Allowed:

MAC prophylaxis with medications other than study drugs (5-day washout period required).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Pulmonary tuberculosis.
• Infections requiring the use of disallowed medications.
• Serious diseases that introduce undue risks for adverse reactions to study medication.

Concurrent Medication:

Excluded:

• Terfenadine.
• Treatment for pulmonary TB.
• Study drugs from an outside source.
• Medications with anti-MAC activity (i.e., amikacin, ciprofloxacin, clofazimine, rifampin, and rifabutin).

Patients with the following prior conditions are excluded:

• History of hypersensitivity to rifabutin, rifampin, clarithromycin, erythromycin, azithromycin, or ethambutol.
• Previous episode of uveitis.

Prior Medication:

Excluded:

• Prophylactic treatment for MAC with rifabutin or any of the study medications.
• Azithromycin within the 3 weeks prior to randomization.
• Any investigational drug during the 4 weeks prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Anderson Clinical Research
• Collaborators: Hoechst Marion Roussel

Study record dates

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: August 1, 1997

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Bacteremia; rifapentine; AIDS-Related Opportunistic Infections; Mycobacterium avium-intracellulare Infection; Azithromycin; Clarithromycin; Antitubercular Agents
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Sepsis; Actinomycetales Infections; Mycobacterium Infections, Nontuberculous; Infections; Communicable Diseases; Mycobacterium Infections; Bacteremia; Mycobacterium avium-intracellulare Infection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Protein Synthesis Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Rifapentine; Clarithromycin; Azithromycin; Ethambutol
• Other Study ID Numbers: 275A; 000473PR0018; 96ACR-HMD1