The Safety and Effectiveness of Rifabutin, Combined With Clarithromycin or Azithromycin, in HIV-Infected Patients

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00001023

Collaborator

(none)

Enrollment

Locations

8.3

Patients Per Site

Study Details

Study Description

Brief Summary

PER 03/10/94 AMENDMENT: PART B. To determine whether there is an effect on plasma drug levels of azithromycin and rifabutin as measured by changes in the plasma concentration-time curve (AUC) when these drugs are taken concomitantly.

ORIGINAL PRIMARY: To gain preliminary information about the safety and tolerance of clarithromycin and azithromycin in combination with rifabutin (three potential agents against Mycobacterium avium-intracellulare) in HIV-infected patients with CD4 counts < 200 cells/mm3.

ORIGINAL SECONDARY: To determine whether there is an effect on the pharmacokinetics of the macrolide antibiotics or rifabutin when these drugs are taken concomitantly. To monitor the effect of rifabutin therapy on dapsone serum levels in patients taking dapsone for PCP prophylaxis. To monitor the effect of macrolide/rifabutin combination therapies on AZT or ddI serum levels.

Two new macrolide antibiotics, clarithromycin and azithromycin, and rifabutin (a rifamycin derivative) have all demonstrated in vitro and in vivo activity against Mycobacterium avium-intracellulare, a common systemic bacterial infection complicating AIDS. Further information is needed, however, regarding the clinical and pharmacokinetic interaction of these drugs used in combination.

Condition or Disease	Intervention/Treatment	Phase
Mycobacterium Avium-intracellulare Infection HIV Infections	Drug: Clarithromycin Drug: Azithromycin Drug: Rifabutin	N/A

Detailed Description

AMENDED 03/10/94 (Part B): Approximately 38 HIV-infected or uninfected subjects are randomized to receive azithromycin or rifabutin (Groups 3 and 4) daily for 14 days, followed by a combination regimen of both drugs for 4 additional weeks. Patients are followed weekly. Pharmacokinetic sampling will be performed on days 14, 15, and 42-45.

ORIGINAL: Sixty-eight patients are randomly assigned to one of four groups (17 patients per group). They receive either clarithromycin or azithromycin in combination with rifabutin on one of two different dosing schedules. Patients receive medication for 6 weeks and undergo follow-up weekly during drug administration and at week 8.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Evaluation of the Safety, Tolerance and Pharmacokinetics of Rifabutin/Clarithromycin Combination and Rifabutin/Azithromycin Combination in HIV-Infected Patients

Actual Study Completion Date :

Jul 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Allowed:

Primary or secondary PCP prophylaxis with TMP/SMX, dapsone, or aerosolized pentamidine.
Any approved therapy for antiretroviral treatment, or antiretroviral therapy available through FDA-sanctioned treatment IND or treatment protocol.

Patients must have:

AMENDED (PART B):

Either HIV infection OR no HIV infection.
CD4 count unspecified.

ORIGINAL:

Documented HIV infection.
CD4 count < 200 cells/mm3 within 90 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

Known Mycobacterium avium-intracellulare (MAI) bacteremia or presence of a clinical syndrome compatible with MAI (i.e., fevers, weight loss, elevated LDH and alkaline phosphatase).
Fever = or > 38.5 deg C (100.4 deg F) within 7 days prior to study entry.

Concurrent Medication:

Excluded:

Acute or chronic use of phenobarbital, carbamazepine, rifampin, dilantin, fluconazole, itraconazole, ketoconazole, ciprofloxacin, beta-blockers, or clarithromycin.
Oral contraceptives.
Acute therapy for an AIDS-related opportunistic infection or malignancy, or other acute medical illness, or infection.
Maintenance therapy for CMV, cryptococcal meningitis, or toxoplasmosis.
Cytotoxic chemotherapy.

Patients with the following prior conditions are excluded:

History of intolerance or hypersensitivity to study drugs, other macrolide antibiotics, or rifampin.
Three or more loose bowel movements per day within 3 months prior to study entry.
Unintentional weight loss >= 5 percent of body weight within 3 months prior to study entry.

Prior Medication:

Excluded:

Rifabutin within 30 days prior to study entry.
Clarithromycin or azithromycin within 14 days prior to study entry.
Acute therapy for an AIDS-related opportunistic infection or malignancy, or other acute medical illness, or infection within 28 days prior to study entry.

Prior Treatment:

Excluded:

Blood transfusions within 1 month prior to study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Arizona / Health Science Ctr	Tucson	Arizona	United States	85724
2	Palo Alto Veterans Affairs Health Care System	Palo Alto	California	United States	94304
3	Davies Med Ctr	San Francisco	California	United States	94114
4	Denver Public Health Dept	Denver	Colorado	United States	802044507
5	Georgetown Univ Med Ctr	Washington	District of Columbia	United States	20007
6	Tulane Univ Med School	New Orleans	Louisiana	United States	701122699
7	Univ of Maryland at Baltimore / Veterans Adm	Baltimore	Maryland	United States	21201
8	Washington Univ School of Medicine	St Louis	Missouri	United States	63108
9	Univ of North Carolina School of Medicine	Chapel Hill	North Carolina	United States	275997215
10	Univ of Rhode Island / Roger Williams Med Ctr	Providence	Rhode Island	United States	02908
11	Med College of Virginia / School of Pharmacy	Richmond	Virginia	United States	232980533