O05.3 A phase ii, randomised, study in adult subjects evaluating the efficacy, safety, and tolerability of single doses of gepotidacin (GSK2140944) for treatment of uncomplicated urogenital gonorrhoea

Introduction Gonorrhoea is currently the second most common bacterial sexually transmitted infection and represents a serious public health threat. The increasing antimicrobial resistance in Neisseria gonorrhoeae (GC) to currently available therapies is driving an urgent need for new novel agents. Gepotidacin (GEP) is a novel, first in class triazaacenaphthylene antibacterial which inhibits bacterial DNA replication. This multicenter (11 US and 1 UK) trial evaluated GEP as a single oral dose in men and women. Methods Patients with signs and symptoms of urogenital gonorrhoea, a prior culture or nucleic acid amplification test (NAAT) positive for GC, a urethral Gram stain with intracellular diplococci, or who had sexual contact with an individual diagnosed with gonorrhoea in the past 14 days were eligible for enrollment. Participants were randomised 1:1 to receive either 1.5g or 3g GEP orally. The primary efficacy endpoint was culture confirmed microbiological eradication at test-of-cure (TOC) visit 3–7 days post dose. Results 106 patients (101 men and 5 women) were randomised and 105 received treatment. Baseline GC isolates were identified in 69 (65%) urogenital, 3 (3%) pharyngeal, and 4 (4%) rectal specimens. Microbiological success was achieved by 97% and 95% of subjects with urogenital GC in the 1.5g and 3g treatment groups, respectively. Isolates from 2 subjects developed resistance to GEP between baseline and TOC. The most common GEP-related AEs were gastrointestinal (diarrhoea, flatulence, abdominal pain and nausea) with the majority being mild or moderate in intensity. Treatment-related AEs of moderate intensity occurred with a higher incidence in the 3g treatment group than the 1.5g treatment group (15% and 10%, respectively). There were no AEs that led to study withdrawal and no SAEs were reported. Conclusions Both the GEP 1.5g and 3g single doses eradicated urogenital GC with microbiological success rates of 29/30 (97%) and 37/39 (95%), respectively. The data support further development of GEP in this indication. Support: This study was supported by GSK (BTZ116576; NCT02294682). This project was funded in whole or in part with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced. Research and Development Authority (BARDA ), under agreement # HHSO100201300011C