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

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.

Community-Acquired Bacterial Pneumonia—Changing Epidemiology, Resistance Patterns, and Newer Antibiotics: Spotlight on Delafloxacin

“…These in vitro and pharmacokinetic-pharmacodynamic findings were largely corroborated in the recent DEFINE-CABP study [103] in which delafloxacin was compared to moxifloxacin, another anti-pneumococcal fluoroquinolone. (62 (11.9%)).…”

“…The phase III CABP (DEFINE-CABP), was a randomized, double-blind, comparator-controlled, multicenter, global study in which patients received a minimum of six IV 300 mg delafloxacin doses (twice daily), with an option to switch to oral 450 mg delafloxacin (twice daily) for up to 20 total doses, or at least three IV moxifloxacin, 400 mg once daily, with an option to switch to oral moxifloxacin (400 mg once daily), for up to ten total doses [103]. The primary efficacy endpoint for the FDA was Early Clinical Response, defined as improvement at 96 h (± 24 h) in at least two of the following: pleuritic chest pain, frequency/ severity of cough, amount/quality of productive sputum, and dyspnea, without worsening of any other symptoms.…”

“…Clinical response was measured at day 4 + 1 day in four different populations with non-inferiority demonstrated in the overall population. However, on examination of the pre-defined sub-groups, those with multi-lobar pneumonia showed a slightly better response with delafloxacin, while in the COPD/asthma cohort there was a significantly improved response in the delafloxacin arm-93.4% success compared with 76.8% in the moxifloxacin group (Table 2) [103].…”

“…DEFINE-CABP study early clinical response outcome by analysis set and subgroup of ITT population (from Horcajada et al[103], with permission from Oxford University Press)…”

<p>Investigational and Experimental Drugs for Community-Acquired Pneumonia: the Current Evidence</p>

“…The efficacy of delafloxacin for CAP was demonstrated in a Phase 3, randomized double-blind trial. 32 In this study iv delafloxacin, with potential to switch to oral delafloxacin, was compared to iv moxifloxacin, with potential to switch to oral moxifloxacin and potential to switch moxifloxacin to iv linezolid for confirmed MRSA. A total of 860 patients with CAP in PORT risk class of II to V were planned to be enrolled and finally 859 were included in the intention-to-treat (ITT) population.…”