1479. Clinical Efficacy and Safety Analysis Evaluating Oral Gepotidacin (GSK2140944) from a Phase IIa Study in the Treatment of Uncomplicated Urinary Tract Infections

Abstract Background Urinary tract infections (UTIs) are very common, with approximately 11% of women >18 years of age experiencing at least 1 episode of acute cystitis per year. Multidrug resistance, typically associated with nosocomial infections, has now emerged at the community level making treatment options for UTIs more difficult. Gepotidacin (GEP), a first-in-class, novel triazaacenaphthylene antibacterial has demonstrated in vitro activity against uropathogens including E. coli and provides high and sustained urine concentrations. It selectively inhibits bacterial DNA replication through a unique mechanism not utilized by any currently approved antibacterial. GEP presents an opportunity to address an unmet medical need and warrants study as a potential new and effective oral treatment for acute cystitis. Methods This Phase IIa single-center study was designed primarily to evaluate plasma and urine pharmacokinetics (PK) of gepotidacin in female participants with acute cystitis. Safety data and clinical and microbiological efficacy of gepotidacin were also assessed as secondary and exploratory endpoints. All participants received oral gepotidacin 1,500 mg BID for 5 days (total of 10 doses) during clinic confinement. Pretreatment and posttreatment PK collections were performed together with safety, efficacy, microbiological, and exploratory assessments throughout the study. Results Summary of Exploratory Endpoints (ITT Population). Clinical Efficacy: All subjects had significant improvement of clinical symptoms (dysuria, frequency, urgency, lower abdominal pain) within 24 to 48 hours of treatment. Most subjects, (20/22; 90.9%) achieved symptom resolution at test of cure (ToC) and follow-up (F/U). Microbiological eradication was achieved independent of baseline CFU’s (see microbiology abstract). Safety Endpoint: Most common AEs involved the GI tract (diarrhea (18/22 [82%] and nausea 17/22 [77%]). Per investigator observation, tolerance to nausea was observed with repeat dosing. No withdrawal due to AE. There were no clinically relevant trends in safety laboratories, ECG, or vital signs. Conclusion This first report of efficacy and safety in the treatment of acute cystitis supports further study of the clinical use of GEP in this indication. Disclosures All authors: No reported disclosures.