Plain Language Summary
What is this summary about?
Gepotidacin is a new oral antibiotic that is under investigation as a treatment for certain infections. This is a summary of two clinical studies of gepotidacin: EAGLE-2 and EAGLE-3 which researched how well gepotidacin works for the treatment of uncomplicated urinary tract infection (uUTI; acute cystitis, a bladder infection), and whether there were any side effects of the drug (any effect of the treatment that was beyond its desired effect). Results from these studies were published in The Lancet in February 2024. Researchers compared gepotidacin with nitrofurantoin,an antibiotic commonly used to treat uUTI. Participants had therapeutic success if they had no symptoms, no infection-causing bacteria growing after treatment, and did not take any other antibiotics. Gepotidacin or nitrofurantoin tablets were taken twice daily for five days. The study participants were females at least 12 years old with a diagnosed uUTI.Together, the studies were done in 15 different countries. The EAGLE-2 study was conducted between October 2019 and November 2022;the EAGLE-3 study was conducted between April 2020 and December 2022.
What are the key takeaways?
A total of 3136 participants were included in the studies and 1201 were evaluated for how effective the drugs were (as they received treatment and had qualifying bacteria expected to respond to nitrofurantoin). In the EAGLE-2 study, gepotidacin was shown to work at least as well as (not worse than) nitrofurantoin: 51% therapeutic success with gepotidacin, 47% with nitrofurantoin. In the EAGLE-3 study, the results favoured gepotidacin over nitrofurantoin:58% therapeutic success with gepotidacin, 44% with nitrofurantoin. Of the side effects reported, most were mild to moderate. No lifethreatening or fatal events occurred. The most common side effects were diarrhoea and nausea. Diarrhoea occurred in 14–18% of participants who took gepotidacin, and 3–4% of participants who took nitrofurantoin; nausea occurred in 8–11% of participants who took gepotidacin and 4% of participants who took nitrofurantoin.
What were the main conclusions reported by the researchers?
In the EAGLE-2 and EAGLE-3 studies, gepotidacin was shown to be an effective treatment for uUTI and was well tolerated by participants.
Key results
In the EAGLE-2 study, gepotidacin was shown to work at least as well as nitrofurantoin. In the EAGLE-3 study, it was shown to work better than nitrofurantoin. Of the side effects reported, most were mild to moderate. No life-threatening or fatal events occurred.
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Acknowledgments
The authors would like to thank the participants, their families, their caregivers, the trial investigators, and their team members at each site that participated in the EAGLE-2 and EAGLE-3 trials, particularly given the challenges of conducting clinical trials during a global pandemic.
Disclosure statement
FW – Advisor to GSK and a principal investigator in a GSK-sponsored study. Speaker of the DFG (German Research Foundation) funded research group BARICADE(FOR5427/1-466687329). Member of the DZIF (German Center for Infection Research. Site: Giessen - Marburg - Langen). CRP, NESO, HM, MP, EJ, JD, AS, DB, JB, SJ – employed by GSK and hold financial equities in GSK. TMH – Advisor to GSK. MK – CEO and founder of Live UTI Free Ltd. PK – Advisor and speaker for GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Medical writing support, under the direction of the authors, was provided by Rosie Robson, MSc, and Niamh Southern, MPhil, of Ashfield MedComms (Manchester,UK), an Inizio company, and was funded by GSK.
Patient reviewers on this PLSP have received honorarium from Future Microbiology for their review work but have no other relevant financial relationships to disclose.
Funding
This manuscript was funded by GSK. GSK supported the writing of the report and the decision to submit for publication (although the ultimate authority over the manuscript lies with the authors). EAGLE-2 was also supported in part with Federal funds from the US Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (HHSO100201300011C), this funder had no role in the decision to publish, or preparation of the manuscript.