Analysis of Pooled Phase III Efficacy Data for Delafloxacin in Acute Bacterial Skin and Skin Structure Infections.

Background: Delafloxacin is an oral or intravenous (IV) antibiotic indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI), including both gram-positive (including methicillin-resistant Staphylococcus aureus [MRSA]) and gram-negative organisms. Chemically distinct from other quinolones, delafloxacin exhibits enhanced potency, particularly against gram-positive pathogens. The integration of efficacy data across the Phase III ABSSSI studies is presented here and allows for additional examination of results across subgroups.

Methods: Results of 2 multicenter, randomized, double-blind trials of 1510 adults with ABSSSI were pooled for this analysis. Subjects in the vancomycin arm received 15 mg/kg, plus 1-2 g of aztreonam every 12 hours. Delafloxacin was dosed at 300 mg IV every 12 hours in Study 302; dosing in Study 303 was 300 mg IV every 12 hours for 3 days, with a mandatory, blinded switch to delafloxacin at 450 mg orally every 12 hours. The primary endpoint was objective response (OR), defined as a ≥20% reduction of lesion spread of erythema area at the primary infection site at 48 to 72 hours (±2 hours), in the absence of clinical failure. Investigator-assessed response, based on the resolution of signs and symptoms at follow-up (FU; Day 14 ± 1) and late follow-up (LFU; Day 21- 28), were secondary endpoints.

Results: In the intent-to-treat analysis set, the OR was 81.3% in the delafloxacin arm and 80.7% in the comparator arm (mean treatment difference 0.8%, 95% confidence interval -3.2% to 4.7). Results for OR in the defined subgroups showed delafloxacin to be comparable to vancomycin/aztreonam. Investigator-assessed success was similar at FU (84.7% versus 84.1%) and LFU (82.0% versus 81.7%). Delafloxacin was comparable to vancomycin/aztreonam in the eradication of MRSA, at 98.1% versus 98.0%, respectively, at FU. The frequencies of treatment-emergent adverse events between the groups were similar.

Conclusions: Overall, IV/oral delafloxacin fixed-dose monotherapy was non-inferior to IV vancomycin/aztreonam combination therapy and was well tolerated in each Phase III study, as well as in the pooled analysis, regardless of endpoint or analysis population.