Early symptom response in patients with uncomplicated urinary tract infection treated with gepotidacin or nitrofurantoin: pooled analysis from two pivotal Phase 3 studies.

Abstract

Uncomplicated urinary tract infections (uUTIs) can cause distressing symptoms seriously impacting daily activities. Early symptom relief during treatment, though fundamental to patients, is often overlooked in clinical trials. Gepotidacin, a new antibacterial agent, was noninferior to the first-line treatment nitrofurantoin in two randomized controlled trials (EAGLE-2 [NCT04020341] and EAGLE-3 [NCT04187144]). The current analysis utilized pooled data from these two trials to evaluate symptom responses during and after treatment in participants with uUTI. Participants were aged ≥12 years with at least two uUTI symptoms, urinary nitrite and/or pyuria, and no complicating factors. Participants were randomized 1:1 to oral gepotidacin (1500 mg) or nitrofurantoin (100 mg), both taken twice daily for 5 days. At baseline (Day 1), on-therapy (OT; Day 2-4), and test-of-cure (TOC; Day 10-13) visits, urinary symptoms were assessed (0-3; none-severe) from which a total score (0-12) was derived. Overall, 3136 participants were randomized (1572 gepotidacin, 1564 nitrofurantoin). Mean (median) baseline symptom scores for gepotidacin and nitrofurantoin arms were 7.1 (7.0) and 7.2 (7.0), respectively; at OT, this decreased to 3.6 (3.0) for both arms. At the OT visit, >80% of participants had clinical improvement/resolution. Among those with baseline symptoms affecting everyday activities (moderate or severe), 53.2% (728/1369) assigned gepotidacin and 53.6% (738/1377) assigned nitrofurantoin reported at OT that symptoms no longer affected everyday activities (mild or absent); at TOC, these percentages were 93.8% (1232/1313) and 93.3% (1254/1344), respectively. Gepotidacin and nitrofurantoin provide meaningful and similar early relief from uUTI symptoms.