File Thomas M, Goldberg Lisa, Das Anita, Sweeney Carolyn, Saviski John, Gelone Steven P, Seltzer Elyse, Paukner Susanne, Wicha Wolfgang W, Talbot George H, Gasink Leanne B
Summa Health, Akron, Ohio.
Nabriva Therapeutics US, Inc., King of Prussia, Pennsylvania.
Clin Infect Dis. 2019 Nov 13;69(11):1856-1867. doi: 10.1093/cid/ciz090.
Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP.
In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5-10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%).
There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference -2.9%, 95% confidence interval [CI] g -8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference -2.6%, 95% CI -8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference -2.5%, 95% CI -8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin.
Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated.
NCT02559310.
来法莫林是一种截短侧耳素类抗生素，对常见的社区获得性细菌性肺炎（CABP）病原体具有活性。来法莫林治疗肺炎评估（LEAP 1）研究是一项全球非劣效性试验，旨在评估来法莫林治疗CABP的疗效和安全性。
在这项双盲研究中，肺炎结局研究团队风险等级≥III的CABP成年患者按1:1随机分组，每12小时静脉注射（IV）150 mg来法莫林或每24小时IV注射400 mg莫西沙星。6剂后，如果符合预先设定的改善标准，患者可改用口服研究药物。如果怀疑有耐甲氧西林金黄色葡萄球菌感染，则分别在莫西沙星或来法莫林中添加利奈唑胺或安慰剂。美国食品药品监督管理局的主要终点是在意向性治疗（ITT）人群中，首次服用研究药物后96±24小时的早期临床反应（ECR）（非劣效界值为12.5%）。欧洲药品管理局的共同主要终点是在改良ITT（mITT）和临床可评估（CE）人群中，最后一剂研究药物后5 - 10天的研究者评估的临床反应（IACR）（非劣效界值为10%）。
共有551例患者随机分组（来法莫林组n = 276；莫西沙星组n = 275）。来法莫林在ECR方面不劣于莫西沙星（分别为87.3%和90.2%；差异 -2.9%，95%置信区间[CI]为 -8.5至2.8）和IACR（mITT分别为81.7%和84.2%；差异 -2.6%，95% CI为 -8.9至3.9；CE分别为86.9%和89.4%；差异 -2.5%，95% CI为 -8.4至3.4）。因治疗中出现的不良事件而停用研究药物的发生率，来法莫林组为2.9%，莫西沙星组为4.4%。
来法莫林在主要疗效终点方面不劣于莫西沙星，且总体安全且耐受性良好。
NCT02559310。
