1688 - Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study

Background: In a previous phase 1b study, ≥ 90% of patients with cystitis treated with omadacycline (OMC), a novel intravenous (IV) and oral aminomethylcycline, achieved clinical success. We assessed the safety and efficacy of OMC vs nitrofurantoin (NIT) for treatment of cystitis in a randomized, adaptive phase 2 study.

Methods: Females ≥18 years with uncomplicated symptomatic cystitis were randomized to oral dose regimens of OMC or NIT for 7 days (NCT03425396; Table 1). Efficacy was assessed for noninferiority by investigator’s assessment of clinical response (IACR) at post-treatment evaluation (PTE; primary endpoint; Day 14). Other endpoints included IACR, microbiologic response, and composite clinical and microbiologic response at end of treatment (EOT) and PTE. Treatment-emergent adverse events (TEAEs) were assessed. Results were reviewed by a data monitoring committee.Table 1


Results: Of 225 patients enrolled, 93.8% completed the study. Baseline (BL) characteristics were similar across groups, except Group 4, which was added late in the study based on blinded review of tolerability. (Table 2). Most patients had moderate BL symptoms of urinary tract infection. Among those with an identified pathogen, the most common species was E. coli. BL minimum inhibitory concentrations (MICs) against E. coli were 0.5 to 8 µg/mL for OMC and < 2 to 64 µg/mL for NIT. Clinical success rates for the intent-to-treat (ITT) population at PTE were high for all groups (OMC 78–88%; NIT 91%; Figure). Microbiologic response rates were higher with NIT vs OMC at PTE (Figure). Noninferiority of OMC to NIT was not met, as the lower limit of the 95% CI for treatment difference exceeded −10% (range −16.8% to −44.1%). OMC was generally well tolerated, with gastrointestinal disorders as the most frequent TEAEs (OMC 22%; NIT 14.8%).Table 2
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Conclusion: In this phase 2 study, clinical success rates were high in the OMC and NIT groups, although no OMC group met noninferiority criteria. Microbiological responses with all doses of OMC were generally lower than in the NIT group, potentially influenced by the higher BL MICs observed in this study compared with the previous phase 1b study. OMC was well tolerated, with a safety profile consistent with its current labeling. Further analyses are needed to fully understand study outcomes.