Biaxin Clinical Trials and Studies

Biaxin Information

Biaxin Clinical Trials and Studies

Mycobacterial Infections Prophylaxis Biaxin Study

A randomized, double-blind Biaxin study (561) compared Biaxin (clarithromycin) 500 mg bid to placebo in patients with CDC-defined AIDS and CD4 counts <100 cells/mcl. This study accrued 682 patients from November 1992 to January 1994, with a median CD4 cell count at study entry of 30 cells/mcl. Median duration of Biaxin (clarithromycin) was 10.6 months vs. 8.2 months for placebo. More patients in the placebo arm than the Biaxin (clarithromycin) arm discontinued prematurely from the study (75.6% and 67.4%, respectively). However, if premature discontinuations due to MAC or death are excluded, approximately equal percentages of patients on each arm (54.8% on clarithromycin and 52.5% on placebo) discontinued study drug early for other reasons. The study was designed to evaluate the following endpoints:

1. MAC bacteremia, defined as at least one positive culture for M. avium complex bacteria from blood or another normally sterile site.
2. Survival.
3. Clinically significant disseminated MAC disease, defined as MAC bacteremia accompanied by signs or symptoms of serious MAC infection, including fever, night sweats, weight loss, anemia, or elevations in liver function tests.

MAC Bacteremia

In patients randomized to Biaxin (clarithromycin), the risk of MAC bacteremia was reduced by 69% compared to placebo. The difference between groups was statistically significant (p<0.001). On an intent-to-treat basis, the one-year cumulative incidence of MAC bacteremia was 5.0% for patients randomized to Biaxin (clarithromycin) and 19.4% for patients randomized to placebo. While only 19 of the 341 patients randomized to Biaxin (clarithromycin) developed MAC, 11 of these cases were resistant to Biaxin (clarithromycin). The patients with resistant MAC bacteremia had a median baseline CD4 count of 10 cells/mm3 (range 2-25 cells/mm3). Information regarding the clinical course and response to Biaxin (clarithromycin) treatment of the patients with resistant MAC bacteremia is limited. The 8 patients who received Biaxin (clarithromycin) and developed susceptible MAC bacteremia had a median baseline CD4 count of 25 cells/mm3 (range 10-80 cells/mm3). Comparatively, 53 of the 341 placebo patients developed MAC; none of these isolates were resistant to Biaxin (clarithromycin). The median baseline CD4 count was 15 cells/mm3 (range 2-130 cells/mm3) for placebo patients that developed MAC.

Treatment

Three randomized Biaxin studies (500, 577, and 521) compared different dosages of Biaxin (clarithromycin) in patients with CDC-defined AIDS and CD4 counts <100 cells/mcl. These studies accrued patients from May 1991 to March 1992. Study 500 was randomized, double-blind; Study 577 was open-label compassionate use. Both studies used 500 and 1000 mg bid doses; Study 500 also had a 2000 mg bid group. Study 521 was a pediatric study at 3.75, 7.5, and 15 mg/kg bid. Study 500 enrolled 154 adult patients, Study 577 enrolled 469 adult patients, and Study 521 enrolled 25 patients between the ages of 1 to 20. The majority of patients had CD4 cell counts <50/mcl at study entry. The studies were designed to evaluate the following end points:

1. Change in MAC bacteremia or blood cultures negative for M. avium.
2. Change in clinical signs and symptoms of MAC infection including one or more of the following: fever, night sweats, weight loss, diarrhea, splenomegaly, and hepatomegaly.

The results for the 500 study are described in Survival. The 577 study results were similar to the results of the 500 study. Results with the 7.5 mg/kg bid dose in the pediatric study were comparable to those for the 500 mg bid regimen in the adult studies.

Study 069 compared the safety and efficacy of Biaxin (clarithromycin) in combination with ethambutol versus clarithromycin in combination with ethambutol and clofazimine for the treatment of disseminated MAC (dMAC) infection. This 24-week study enrolled 106 patients with AIDS and dMAC, with 55 patients randomized to receive Biaxin (clarithromycin) and ethambutol, and 51 patients randomized to receive clarithromycin, ethambutol, and clofazimine. Baseline characteristics between study arms were similar with the exception of median CFU counts being at least 1 log higher in the Biaxin (clarithromycin), ethambutol, and clofazimine arm.

Compared to prior experience with Biaxin (clarithromycin) monotherapy, the two-drug regimen of clarithromycin and ethambutol was well tolerated and extended the time to microbiologic relapse, largely through suppressing the emergence of Biaxin (clarithromycin) resistant strains. However, the addition of clofazamine to the regimen added no additional microbiologic or clinical benefit. Tolerability of both multidrug regimens was comparable with the most common adverse events being gastrointestinal in nature. Patients receiving the clofazimine-containing regimen had reduced survival rates; however, their baseline mycobacterial colony counts were higher. The results of this trial support the addition of ethambutol to Biaxin (clarithromycin) for the treatment of initial dMAC infections but do not support adding clofazimine as a third agent.

Biaxin Information