Volume 32, Issue 1, January 2026, 102829Author links open overlay panel, , , , , , , , ,

Principal investigators of the study

AbstractBackground

Two global Phase 3 trials, EAGLE-2 and EAGLE-3, found gepotidacin non-inferior (and superior in EAGLE-3) to nitrofurantoin for the treatment of uUTI in female participants, with an acceptable safety profile; however, these studies did not include Japanese centers.

Methods

EAGLE-J (NCT05630833; jRCT2031220467) was a Phase 3, randomized, double-blind, active reference study evaluating the efficacy and safety of gepotidacin for the treatment of uUTI in Japan. Eligible participants were females aged ≥12 years with ≥2 uUTI symptoms and urinary nitrite or pyuria. Participants were randomly assigned (3:1) oral gepotidacin (1500 mg) or nitrofurantoin (100 mg) twice daily for 5 days. To bridge data, consistency of therapeutic response at test-of-cure (day 10–13) in the gepotidacin arm of EAGLE-J with EAGLE-2/EAGLE-3 was assessed in participants with qualifying nitrofurantoin-susceptible uropathogens (≥105 colony-forming units/mL). Therapeutic success comprised clinical (symptom resolution) and microbiological success (eradication). Consistency was claimed if the therapeutic success rate in EAGLE-J was greater than the consistency threshold predicted from EAGLE-2/EAGLE-3.

Findings

Overall, the primary analysis included 108 participants (83 gepotidacin, 25 nitrofurantoin). At test-of-cure, gepotidacin therapeutic success was 83.1 % (69/83), exceeding the consistency threshold (48.2 %). Adverse events were mostly mild-to-moderate; common adverse events were diarrhea (gepotidacin: 60 %, 168/281; nitrofurantoin: 8 %, 7/93) and nausea (gepotidacin: 12 %, 35/281; nitrofurantoin: 2 %, 2/93). No fatalities occurred.

Interpretation

Gepotidacin therapeutic success at test-of-cure was consistent between EAGLE-J and EAGLE-2/-3. Gepotidacin has potential as a valuable oral treatment option for uUTI in Japan. No new safety signals were identified.

Keywords

Gepotidacin

Urinary tract infection

Japan

AbbreviationsAChE-I

acetylcholinesterase inhibition

AESI

adverse events of special interest

AMR

antimicrobial resistance

CDAD

Clostridioides difficile-associated diarrhea

eCRF

electronic case report form

ESBL+

extended-spectrum β-lactamase producing

FDA

Food and Drug Administration

FQ-R

fluoroquinolone-resistant

MedDRA

Medical Dictionary for Regulatory Activities

micro-ITT MDR

microbiological intent-to-treat multidrug-resistant

micro-ITT NTF-S (IA set)

microbiological intent-to-treat nitrofurantoin-susceptible interim analysis set

micro-ITT NTF-S

microbiological intent-to-treat nitrofurantoin-susceptible

QTcB

Corrected QT Interval Bazett

QTcF

Corrected QT Interval Fridericia

SAE

serious adverse events

TEAE

treatment-emergent adverse event

uUTI

uncomplicated urinary tract infection

© 2025 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd.