A Phase-3 Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults with Community-acquired Bacterial Pneumonia (DEFINE-CABP)

Abstract

Abstract Background The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin’s shape and charge profile uniquely impacts its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin to moxifloxacin for the treatment of CABP. Methods A randomized, double-blind, comparator-controlled, multicenter, global Phase 3 study compared the efficacy and safety of delafloxacin 300 mg BID or moxifloxacin 400 mg QD in adults with CABP. The primary endpoint was early clinical response (ECR) defined as improvement at 96 (± 24) hours after first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed. Results In the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group. Conclusions IV/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for grampositive, gramnegative, and atypical pathogens.