Challenges in Managing Gonorrhea and New Advances in Prevention

Ewers, Evan C; Curtin, John M.; Ganesan, Anuradha

doi:10.1016/j.idc.2023.02.004

Cited by 2 publications

(1 citation statement)

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“…Global surveillance of NG by the WHO in 2017–2018, which included data from 73 countries, showed widespread AMR [ 13 ]. Specifically, ciprofloxacin resistance was extremely high (present in all reporting countries), resistance to azithromycin was reported in 84% of countries and rapidly increasing, and resistance to ceftriaxone and cefixime was emerging (in 31% and 47% of countries, respectively) [ 4 , 13 , 14 ]. Over time, resistance to the above first-line therapies, and other historical treatments (e.g., fluoroquinolones, macrolides such as azithromycin, and β-lactams such as penicillin and tetracycline) has increased, and now the CDC recommends 500 mg intramuscular ceftriaxone as the sole effective treatment for gonorrhea [ 12 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Gepotidacin as Treatment of Uncomplicated Urogenital Gonorrhea (EAGLE-1): Design of a Randomized, Comparator-Controlled, Phase 3 Study

Perry,

Scangarella-Oman,

Millns

et al. 2023

Infect Dis Ther

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Introduction Gonorrhea, caused by Neisseria gonorrhoeae (NG), is the second most common bacterial sexually transmitted infection (STI). Rates of antimicrobial resistance to standard care are increasing worldwide, with many antibiotic classes now ineffective against NG. Gepotidacin is a first-in-class, bactericidal, triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by inhibition of two enzymes, where a single target-specific mutation does not significantly impact susceptibility. Gepotidacin confers activity against NG, including most strains resistant to marketed antibiotics. Here, we describe the design of a phase 3 clinical trial (EAGLE-1; NCT04010539) evaluating gepotidacin for the treatment of uncomplicated urogenital gonorrhea. Methods This phase 3, randomized, multicenter, sponsor-blinded, noninferiority study across six countries is comparing the efficacy of gepotidacin with ceftriaxone plus azithromycin in 400 patients with uncomplicated urogenital gonorrhea (microbiological intent-to-treat population) and assessing the safety of gepotidacin in approximately 600 patients (intent-to-treat population). Eligible participants 12 years of age or older with clinical suspicion of urogenital gonococcal infection and a NG-positive urogenital sample and/or purulent discharge are randomized 1:1 to receive oral gepotidacin (2 × 3000 mg 10–12 h apart) or ceftriaxone (500 mg, intramuscular) plus azithromycin (1 g, oral). The primary endpoint is culture-confirmed bacterial eradication of NG from the urogenital site at the test-of-cure (days 4–8) visit. Planned Outcomes This trial was designed in accordance with US Food and Drug Administration (2015) and European Medicines Agency (2011) guidance, particularly the primary endpoint and microbiological evaluability requirements. This study will help characterize the risk–benefit profile of gepotidacin for treating uncomplicated urogenital gonorrhea. Gepotidacin is an important potential treatment for gonorrhea to help address the urgent unmet need of multidrug resistance and the increasingly limited number of oral treatment options. Trial Registration ClinicalTrials.gov identifier, NCT04010539. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00862-6.

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