2232. A Global Phase 3 Study of Delafloxacin (DLX) Compared with Moxifloxacin (MOX) in Patients with Community-acquired Bacterial Pneumonia (CABP)

Abstract

BackgroundDLX is an IV/oral fluoroquinolone with no QT restrictions, and activity against Gram-positive, Gram-negative and atypical pathogens. DLX is approved for treatment of ABSSSI including those due to MRSA and Gram-negative pathogens. A Phase 3 trial of patients with CABP was recently completed.MethodsGlobal active-comparator double-blind trial; adults with CABP with at least 2 clinical symptoms, physical signs, and radiographic evidence of pneumonia. Randomized 1:1 to DLX or MOX treatment for 5–10 days. Randomization stratified by PORT Class, history of COPD/asthma, and prior single-dose antibiotic use (limit 25%). Patients received a minimum of 3 days IV treatment, then were switched to oral at MD discretion. The primary endpoint for FDA was the Early Clinical Response (ECR): improvement at 96 hours after first dose of study drug in at least 2 of the baseline symptoms in the Intent to Treat (ITT) population.Results859 patients were randomized; both groups were comparable. Patient characteristics: mean age 60 (range 18–93, 21% ≥ age 75); 58.7% male; 28.6% multi-lobar pneumonia; 26.8% PORT class IV/V. Bacterial pathogens were identified in 60.5% at baseline; most commonly S. pneumoniae, as well as S. aureus, atypicals and Gram-negatives. Patients received treatment ~ 8.5 days (6.3 days of IV, 2.2 days oral). DLX was non-inferior to MOX in ECR 88.9% DLX vs. 89.0% MOX [∆−0.2 (CI -4.4, 4.1)] in the ITT population; ECR in the evaluable population was 91.1% DLX vs. 91.8% MOX [∆−0.6 (CI -4.5, 3.2)]. Day 28 Mortality was 1.9% DLX vs. 1.4% MOX. In the micro evaluable population, DLX was comparable to MOX in eradication, 92.5% DLX vs. 93.5% MOX at Test of Cure 5–10 days after treatment, [∆ −1.0 (CI -5.8, 3.6)]. 30.5% DLX and 26.2% MOX patients had ≥1 treatment-emergent adverse events (AEs). The most common DLX AEs were diarrhea and transaminase elevations, which were mild-to-moderate and did not routinely lead to discontinuation (DC). Treatment DC due to treatment-related AEs was seen in 9 DLX and 4 MOX patients. There were no potential QT AEs with DLX.ConclusionIV/oral DLX was comparable to IV/oral MOX for treatment of CABP in patients. DLX has no preclinical signals for QT prolongation and has no QT prolongation in a validated challenge study. DLX appears effective and well tolerated in patients with CABP.Disclosures All authors: No reported disclosures.