首页 / 院系成果 / 成果详情页

Safety and pharmacokinetics of CL-197, a potent compound with low cytotoxicity against HIV-1: a randomized, double-blind, placebo-controlled, first-in-human phase 1 clinical trial 期刊论文

编号：

9F3849FD54C76F41DB54B666CEB37FC8
作者：

Guo, Yuming#^[1,2]Li, Yonggang^[1];Zhao, Pan^[1];Bi, Jingfeng^[1];Gou, Chaoyun^[3];Chuai, Zhengran^[1];Yu, Shuangjie^[1];Zhang, Renjie^[1];Du, Jinfa^[4];Ou, Yi^[4];Xu, Ruonan^[1];Guo, Na*^[4]Wang, FuSheng*^[1]Li, Yuanyuan*^[1,2]
语种：

英文
期刊：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY ISSN：0066-4804 2026 年 ; 2026 SEP 4
收录：
关键词：

HIV CL-197 pharmacokinetics phase 1 clinical trial
摘要：

HIV infection remains a critical global public health concern. A potential long-acting therapeutic agent, 4 ''-ethynyl-2-fluoroadenosine analog 1c (CL-197), was investigated in a first-in-human phase 1 clinical trial. This single-center, randomized, double-blind, dose-escalation, placebo-controlled study assessed the safety and pharmacokinetics (PKs) of five doses of CL-197 (1, 10, 30, 60, and 100 mg) in healthy adults aged 18-45 years. The 1 mg group was open-label (n = 4), while the other groups were randomized 4:1 to CL-197 or placebo. The primary endpoints were safety and tolerability. The PK evaluation involved the characterization of systemic exposure parameters (based on plasma drug concentrations and peripheral blood mononuclear cell [PBMC] drug concentrations) and urinary excretion parameters. CL-197 was well tolerated at all dose levels. The most frequently reported adverse reactions were sinus arrhythmia, followed by decreased apolipoprotein B, decreased blood iron, increased triglycerides, and elevated low-density lipoprotein. Plasma PKs showed dose-proportional exposure, with a mean time to maximum plasma concentration (Tmax) of 0.50-1.00 h. As the dose increased, the elimination time was prolonged. The plasma drug concentrations were approximately dose-proportional, whereas AUC 0-t and AUC 0-infinity exhibited non-linear characteristics within the range of 1-100mg, with the mean elimination half-life (t1/2) increasing from 1.39 to 10.20 h across doses. The mean t1/2 in PBMCs was 61.29 h and 43.80 h in the 30 mg and 60 mg dose groups, respectively, and the median Tmax was 12 h. In conclusion, a single administration of CL-197 demonstrated an acceptable safety profile in younger adults. The intracellular CL-197-TP in PBMCs had a long half-life, providing preliminary support for the potential use of extended dosing intervals in further development.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05944848.
推荐引用方式
GB/T 7714：

Guo Yuming,Li Yonggang,Zhao Pan, et al. Safety and pharmacokinetics of CL-197, a potent compound with low cytotoxicity against HIV-1: a randomized, double-blind, placebo-controlled, first-in-human phase 1 clinical trial [J].ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2026.
APA：

Guo Yuming,Li Yonggang,Zhao Pan,Bi Jingfeng,&Li Yuanyuan.(2026).Safety and pharmacokinetics of CL-197, a potent compound with low cytotoxicity against HIV-1: a randomized, double-blind, placebo-controlled, first-in-human phase 1 clinical trial .ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.
MLA：

Guo Yuming, et al. "Safety and pharmacokinetics of CL-197, a potent compound with low cytotoxicity against HIV-1: a randomized, double-blind, placebo-controlled, first-in-human phase 1 clinical trial" .ANTIMICROBIAL AGENTS AND CHEMOTHERAPY(2026).
入库时间：

2026/9/16 11:00:17
更新时间：

2026/9/16 11:00:17

浏览次数：3  下载次数：0

分享到：

浏览次数：3

下载次数：0

打印次数：0