Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Administration JMKX003142 in Chinese Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Single, and Multiple Ascending Dose Phase I Clinical Trial

作者：Cheng Cui, Jixiang Zhu, Zhiping Liu, Jingyao Liu, Xiaomin Huang, Yi Liu, Jingqiu Hu, Lingli Zhang, Xue Zhang (166886), Yila Sha, Dongyang Liu, Haiyan Li · 发表于：Drug Design Development and Therapy · 年份：2026 · DOI：10.2147/dddt.s583445 · 研究领域：Statistical Methods in Clinical Trials、Cancer Treatment and Pharmacology、Pharmacogenetics and Drug Metabolism

Purpose: This study is the first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of single ascending doses (SAD) and multiple ascending doses (MAD) of JMKX003142 injection in healthy Chinese subjects. Patients and Methods: In this Phase I, randomized, double-blind, placebo-controlled study, 48 subjects in the SAD (0.1– 6 mg) study received intravenous injection of JMKX003142 or placebo in ascending dose. Thirty subjects in the MAD (1– 4 mg) study received an intravenous injection of JMKX003142 or placebo once a day for five consecutive days. The primary endpoint was the safety and tolerability of JMKX003142 injection, with the secondary and exploratory endpoints focusing on its PK and PD profiles, respectively. Results: The JMKX003142 injection exhibited favourable safety and tolerability, with all treatment-emergent adverse events (TEAEs) being mild. No serious adverse events, deaths or discontinuations due to TEAEs were observed. Following single and multiple intravenous injections of JMKX003142, the maximum concentration (C max ) and area under plasma concentration–time curve (AUC) of JMKX003142 and its metabolites increased with dose level, with increases in C max being dose-proportional. In 1 mg or higher dose group of SAD study, the mean terminal half-life (t 1/2 ) of JMKX003142 was between 5.2 and 12.7 h. Following multiple intravenous injections of JMKX003142, the t 1/2 of JMKX003142 was determined to rang...