Abstract
Background
Two large Phase 3 trials showed that gepotidacin, a first-in-class oral triazaacenaphthylene bactericidal antibiotic, was efficacious in treating uncomplicated urinary tract infection (uUTI) in females and had an acceptable safety profile consistent with prior gepotidacin trials. We now present a pooled analysis of the EAGLE-2 and EAGLE-3 trials to evaluate gepotidacin efficacy and safety in patient subgroups.
Methods
Data were pooled from EAGLE-2 and EAGLE-3, near identical global, Phase 3, randomized, double-blind, double-dummy, active-controlled non-inferiority trials comparing oral gepotidacin (1500mg) to nitrofurantoin (100mg), both twice daily for 5 days. Females aged ≥ 12 years with ≥ 2 uUTI symptoms were eligible. Therapeutic success (combined clinical and microbiological success) was determined at the test-of-cure visit (Day 10–13) for patient subgroups – age, geographic region, history of recurrent uUTI, diabetes, and renal function. Efficacy subgroup analyses were conducted in the pooled microbiological intent-to-treat population of patients with baseline uropathogens (≥ 105 CFU/mL) susceptible to nitrofurantoin (micro-ITT NTF-S) and were adjusted for study. Pooled adverse event (AE) data for the overall population are presented.
Results
Both studies stopped early for efficacy (per independent data monitoring committee review). Among 1201 patients in the pooled micro-ITT NTF-S population, mean age was 51.5 years; 54% were aged > 50 years (Table 1). Across subgroups, differences in therapeutic success numerically favored gepotidacin vs nitrofurantoin (Table 2). Treatment differences were higher for > 50 years vs other age groups and for mild renal impairment vs normal renal function, and were similar within other subgroups. AEs were reported in 35% (gepotidacin) and 23% (nitrofurantoin) of patients (Table 3); most were mild to moderate and gastrointestinal in nature. There were few serious AEs.
Conclusion
Gepotidacin generally demonstrated consistent therapeutic efficacy in patient subgroups, including patients aged > 50 years and those with a history of recurrent uUTI (subgroups at higher risk of treatment failure). There were no new or concerning safety signals. Gepotidacin has potential as a novel oral treatment for uUTI in key patient subgroups.
Disclosures
Thomas M. Hooton, MD, GSK: Advisor/Consultant Caroline R. Perry, PhD, GSK: Employee and shareholder Salim Janmohamed, MD, GSK: Employee and shareholder Amanda Sheets, PhD, GSK: Employee and shareholder Jeremy Dennison, MD, GSK: Employee and shareholder Helen Millns, PhD, GSK: Employee and shareholder Emily Jarvis, MSc, GSK: Employee and shareholder Chun Huang, PhD, GSK: Employee and shareholder