Phase 3 safety comparisons for 1.0% azithromycin in polymeric mucoadhesive eye drops versus 0.3% tobramycin eye drops for bacterial conjunctivitis

Abstract

Purpose: To compare the safety and tolerability of 1.0% azithromycin in a polymeric mucoadhesive delivery system with 0.3% tobramycin ophthalmic solution for the treatment of bacterial conjunctivitis.

Methods: This study was a prospective, randomized, active-controlled, double-masked, phase 3 trial conducted from August 6, 2004, to October 6, 2005, at 47 sites. Subjects with a clinical diagnosis of bacterial conjunctivitis were randomly assigned to receive either 1% azithromycin in DuraSite (AzaSite; InSite Vision, Alameda, CA) (n = 365) or 0.3% tobramycin (n = 378). Both groups received masked medication four times daily for 5 days, but participants received an active dose of 1% azithromycin in DuraSite only twice a day on days 1 and 2 and daily on days 3 to 5. Conjunctival cultures were taken, and ocular signs and symptoms were evaluated at baseline and at two follow-up visits.

Results: A total of 743 patients were randomized, and 710 (96%) completed the trial. Both study medications were well tolerated. The most frequently observed ocular adverse events in the azithromycin group were eye irritation (1.9%), conjunctival hyperemia (1.1%), and worsening bacterial conjunctivitis (1.1%). These rates compared favorably with those obtained with tobramycin. Rates of microbial eradication (an efficacy parameter) and bacterial infection recurrence (a safety parameter) were the same in both groups.

Conclusions: This is the first report of the safety and tolerability of a commercially manufactured preparation of azithromycin for ophthalmic use. Azithromycin 1% in DuraSite is safe and can be administered in a regimen of less frequent doses than can tobramycin, while producing an equivalent clinical outcome. The formulation is well tolerated in patients over the age of 1 year for the eradication of bacteria commonly associated with conjunctivitis. (ClinicalTrials.gov number, NCT00105469.).