美国葛兰素史克公司Caroline Perry团队研究了口服Gepotidacin治疗无并发症泌尿生殖道淋病的疗效与安全性。这一研究成果发表在2025年4月14日出版的《柳叶刀》杂志上。

Gepotidacin是一种抑制细菌DNA复制的一流杀菌三氮杂萘类抗菌药物，在治疗无并发症的尿路感染中显示出有效和良好的耐受性。研究组评价了Gepotidacin治疗无并发症泌尿生殖淋病的疗效和安全性。

EAGLE-1 （NCT04010539）是一项3期、开放标签、受试者盲法、多中心、非效性研究，评估口服Gepotidacin（两次3000 mg剂量，间隔10-12小时）与500 mg肌肉注射头孢曲松加1g口服阿奇霉素治疗淋病的疗效。符合条件的参与者年龄在12岁及以上，体重超过45公斤，怀疑患有无并发症的泌尿生殖系统淋病（包括粘液脓性分泌物），淋病奈瑟菌实验室检测阳性，或两者兼有。参与者按1:1的比例随机分配到每个治疗组，按性别（出生时原始的泌尿生殖器解剖结构）、性取向（男男性行为者[MSM]、男女性行为者[MSW]和女性）组合和年龄组（18岁、≥18至65岁或65岁）分层。主要疗效终点是微生物学上的成功，定义为在治愈试验时（第4-8天）从泌尿生殖体部位培养确认的淋病奈瑟菌的细菌根除。非劣效性裕度预先设定为-10%。主要结局在微生物意向治疗（micro-ITT）人群中进行评估，所有参与者随机分配到研究治疗组，接受至少一剂研究治疗，并从泌尿生殖标本的基线培养中分离出头孢曲松敏感的淋病奈瑟菌。安全人群包括所有接受过一剂或多剂任何研究治疗的参与者。

2019年10月21日至2023年10月10日期间，628名参与者被随机分配（每个治疗组314名）。总体而言，628名参与者中有39人（6%）过早终止研究（Gepotidacin组20人，头孢曲松加阿奇霉素组19人），主要原因是随访失败。微itt人群包括406名参与者（吉波替达素组202名，头孢曲松加阿奇霉素组204名）。micro-ITT人群中的大多数参与者为男性（372人[92%]对34人[8%]对女性），MSM参与者的比例（290人[71%]）高于MSW参与者（82人[20%]）。参与者主要是白人（299人[74%]）或黑人或非裔美国人（61人[15%]），其中70人（17%）认为自己是西班牙裔或拉丁裔。初步的治愈试验微生物反应分析结果显示，Gepotidacin组的微生物治疗成功率为92.6%（202例患者中有187例），头孢曲松加阿奇霉素组的微生物治疗成功率为91.2%（204例患者中有186例[86.4 ~ 97.4]）（调整后治疗差异为- 0.1%）。Gepotidacin不逊于头孢曲松加阿奇霉素。在两组的治愈试验中均未观察到泌尿生殖道N型淋病菌的细菌持久性。Gepotidacin组不良事件及药物相关不良事件发生率较高，主要为胃肠道不良事件，且几乎均为轻度或中度。两组均未发生与治疗相关的严重或严重不良事件。

研究结果表明，Gepotidacin治疗泌尿生殖系统淋病优于头孢曲松+阿奇霉素，无新的安全性问题，为无并发症的泌尿生殖系统淋病提供了一种新的口服治疗选择。

附：英文原文

Title: Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhoea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study

Author: Jonathan D C Ross, Janet Wilson, Kimberly A Workowski, Stephanie N Taylor, David A Lewis, Sally Gatsi, William Flight, Nicole E Scangarella-Oman, Charles Jakielaszek, Dan Lythgoe, Marcy Powell, Salim Janmohamed, Judith Absalon, Caroline Perry

Issue&Volume: 2025-04-14

Abstract: Background

Gepotidacin, a first-in-class, bactericidal, triazaacenaphthylene antibacterial that inhibits bacterial DNA replication, was shown to be efficacious and well tolerated in the treatment of uncomplicated urinary tract infections. We evaluated the efficacy and safety of gepotidacin for the treatment of uncomplicated urogenital gonorrhoea.

Methods

EAGLE-1 (NCT04010539) was a phase 3, open-label, sponsor-blinded, multicentre, non-inferiority study evaluating oral gepotidacin (two 3000 mg doses administered 10–12 h apart) compared with 500 mg intramuscular ceftriaxone plus 1 g oral azithromycin for the treatment of gonorrhoea. Eligible participants were aged 12 years and older, had a bodyweight over 45 kg, and had suspected uncomplicated urogenital gonorrhoea (including mucopurulent discharge), a positive laboratory test for Neisseria gonorrhoeae, or both. Participants were randomly allocated in a 1:1 ratio to each treatment group, stratified by sex (original urogenital anatomy at birth) and sexual orientation (men who have sex with men [MSM], men who have sex with women [MSW], and female) in combination, and age group (age <18 years, ≥18 to 65 years, or >65 years). The primary efficacy endpoint was microbiological success, defined as culture-confirmed bacterial eradication of N gonorrhoeae from the urogenital body site at test-of-cure (days 4–8). The non-inferiority margin was prespecified at –10%. The primary outcome was assessed in the microbiological intention-to-treat (micro-ITT) population, all participants randomly allocated to a study treatment who received at least one dose of their study treatment and had confirmed ceftriaxone-susceptible N gonorrhoeae isolated from the baseline culture of their urogenital specimen. The safety population comprised all participants who received one or more doses of any study treatment.

Findings

Between Oct 21, 2019, and Oct 10, 2023, 628 participants were randomly allocated (314 allocated to each treatment group). Overall, 39 (6%) of 628 participants discontinued the study prematurely (20 in the gepotidacin group and 19 in the ceftriaxone plus azithromycin group), with the primary reason being lost to follow-up. The micro-ITT population included 406 participants (202 in the gepotidacin group and 204 in the ceftriaxone plus azithromycin group). Most participants in the micro-ITT population were male (372 [92%] vs 34 [8%] female), and there was a higher percentage of participants who were MSM (290 [71%]) compared with participants who were MSW (82 [20%]). Participants were predominantly White (299 [74%]) or Black or African American (61 [15%]), with 70 (17%) identifying as Hispanic or Latino. Results of the primary analysis of microbiological response at test-of-cure demonstrated microbiological success rates of 92·6% (187 of 202 [95% CI 88·0 to 95·8]) in the gepotidacin group and 91·2% (186 of 204 [86·4 to 94·7]) in the ceftriaxone plus azithromycin group (adjusted treatment difference –0·1% [95% CI –5·6 to 5·5]). Gepotidacin was non-inferior to ceftriaxone plus azithromycin. No bacterial persistence of urogenital N gonorrhoeae was observed at test-of-cure for either group. The gepotidacin group had higher rates of adverse events and drug-related adverse events, mainly due to gastrointestinal adverse events, and almost all were mild or moderate. No treatment-related severe or serious adverse events occurred in either group.

Interpretation

Gepotidacin demonstrated non-inferiority to ceftriaxone plus azithromycin for urogenital N gonorrhoeae, with no new safety concerns, offering a novel oral treatment option for uncomplicated urogenital gonorrhoea.

DOI: 10.1016/S0140-6736(25)00628-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00628-2/abstract