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.

Condition	Treatment or Intervention	Phase
Mycobacterium avium-intracellulare Infection HIV Infections	Drug: Rifapentine  Drug: Ethambutol hydrochloride  Drug: Clarithromycin  Drug: Azithromycin	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

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

Study ID Numbers:  275A; 000473PR0018; 96ACR-HMD1
Record last reviewed:  August 1997
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002192
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08