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

Juan P Horcajada, Robert A Salata, Rodolfo Álvarez-Sala, Floarea Mimi Nitu, Laura Lawrence, Megan Quintas, Chun-Yen Cheng, Sue Cammarata, DEFINE-CABP Study Group, Juan P Horcajada, Robert A Salata, Rodolfo Álvarez-Sala, Floarea Mimi Nitu, Laura Lawrence, Megan Quintas, Chun-Yen Cheng, Sue Cammarata, DEFINE-CABP Study Group

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 impact its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin with 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 twice daily or moxifloxacin 400 mg once daily in adults with CABP. The primary end point was early clinical response (ECR), defined as improvement at 96 (±24) hours after the 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 that were 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: Intravenous/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for Gram-positive, Gram-negative, and atypical pathogens.

Clinicaltrialsgov identifier: NCT03534622.

Keywords: CABP; delafloxacin; fluoroquinolone; moxifloxacin; pneumonia.

© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Subject disposition and analysis populations. aOne subject was mistakenly randomized into the interactive voice and web response system but did not provide informed consent; therefore, this subject was not included in the intent-to-treat population. bCompleted the study through TOC. Abbreviations: AE, adverse event; ECR, early clinical response; EOT, end of treatment; PK, pharmacokinetics; TOC, test of cure.
Figure 2.
Figure 2.
Early clinical response by analysis set and subgroup (ITT population). Difference was the difference in ECR response rates (delafloxacin treatment group minus moxifloxacin treatment group). The CIs were calculated using the Miettinen-Nurminen method without stratification. Abbreviations: CE, clinically evaluable; CI, confidence interval; ECR, early clinical response; ITT, intent-to-treat; LCL, 95% lower confidence limit; ME, microbiologically evaluable; MITT, microbiological intent-to-treat; UCL, 95% upper confidence limit.
Figure 3.
Figure 3.
Clinical outcome at test of cure by analysis set and subgroup (ITT population). Difference was the difference in ECR response rates (delafloxacin treatment group minus moxifloxacin treatment group). The CIs were calculated using the Miettinen-Nurminen method without stratification. Abbreviations: CE, clinically evaluable; CI, confidence interval; ECR, early clinical response; ITT, intent-to-treat; LCL, 95% lower confidence limit; ME, microbiologically evaluable; MITT, microbiological intent-to-treat; UCL, 95% upper confidence limit.

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