A first-in-human phase I study to evaluate the safety, tolerability, and pharmacokinetics of a novel anti-influenza agent suraxavir marboxil in healthy Chinese subjects

作者：Qingqing Wu, Lang Lv, Shou‐Sheng Yan, Yijun Wang, Qian Chen, Wenjing Xu, Yun Liu, Wei Wang, Jingying Jia, Chen Yu, Jingjing Chen, Yanmei Liu · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2025 · DOI：10.1128/aac.00685-25 · 被引用次数：2 · 研究领域：Influenza Virus Research Studies、Respiratory viral infections research、Hepatitis C virus research

ABSTRACT Suraxavir marboxil (GP681) is a prodrug of a novel polymerase acidic protein inhibitor, and its metabolite GP1707D07 prevents the replication of influenza virus by selectively inhibiting the cap-dependent nucleic acid endonuclease of influenza virus. This study evaluates the safety, tolerability, and pharmacokinetics of suraxavir marboxil after a single dose and assesses the effect of a high-fat, high-calorie meal on the pharmacokinetics of suraxavir marboxil in healthy Chinese subjects. The study included two parts: single ascending-dose study (SAD) and food effect study (FE). In SAD, subjects were randomized to single-dose suraxavir marboxil (20, 40, 60, or 80 mg) or placebo. In FE, subjects ( n = 16) were randomized to single-dose suraxavir marboxil 40 mg in fasting and fed states. Safety assessment and sample collection were in accordance with the protocol. Suraxavir marboxil was well tolerated in healthy Chinese subjects in both SAD and FE, and all adverse events recovered without treatment after discontinuation of suraxavir marboxil. In SAD, after administration of suraxavir marboxil in the dosage range of 20–80 mg, the time to maintain the clinically defined effective target blood concentration is about 72–136 h. In FE, a high-fat, high-calorie meal reduced C max by approximately 19% and AUC 0–∞ by approximately 15%. Suraxavir marboxil was well tolerated in healthy Chinese subjects. Based on the safety and pharmacokinetic data, 20–80 mg single oral dosing was ...