Efficacy and safety of single dose oral delafloxacin compared with intramuscular ceftriaxone for uncomplicated gonorrhea treatment: an open-label, non-inferiority, Phase 3, multicenter, randomized study.

We evaluated single oral dose delafloxacin versus single intramuscular (IM) ceftriaxone in participants with uncomplicated urogenital gonorrhea (primary objective). Secondary objectives included the efficacy, safety, and tolerability of delafloxacin versus ceftriaxone for uncomplicated urogenital, rectal, and/or pharyngeal gonorrhea.In this open-label, multicenter study, 460 participants at 25 study centers were randomized (2:1) to receive a single 900mg oral dose of delafloxacin or 250mg IM ceftriaxone. N. gonorrhoeae culture, nucleic acid amplification test (NAAT) and clinical responses were evaluated. The primary efficacy endpoint was the urogenital microbiological cure in the urogenital microbiological intention-to-treat (UMITT) population; non-inferiority (NI) was assessed using a 10% NI margin.In the UMITT population, urogenital cure rates for delafloxacin were 85.1% (194/228) vs 91.0% (91/100) for ceftriaxone [95% CI -13.18% to 1.36%]. As the lower bound of the CI exceeded the pre-specified -10% NI margin, delafloxacin did not demonstrate non-inferiority to ceftriaxone. Treatment failures were more often associated with N. gonorrhoeae with higher delafloxacin minimum inhibitory concentration (MIC) values. In microbiologically evaluable participants, failure occurred in 1 of 177 (0.6%) urogenital infections caused by isolates with delafloxacin MICs <0.008 μg/mL, and 31 of 48 (64.6%) infections caused by isolates with delafloxacin MICs >0.008 μg/mL. Gastrointestinal adverse events (AEs) were common with 900mg of delafloxacin, and typically included mild to moderate diarrhea, flatulence, nausea, and vomiting. The most common AE was diarrhea in both treatment groups.A single 900mg dose of delafloxacin is not a reliable treatment for uncomplicated urogenital gonorrhea. Treatment failures were common in infections caused by N. gonorrhoeae with delafloxacin MICs >0.008 μg/mL. Additional testing with alternative dosing regimens could be considered.ClinicalTrials.gov Identifier: NCT02015637.