TQ-A3334 是一种口服 Toll 样受体 7 激动剂，在健康个体中的安全性、药代动力学和药效学研究。
Safety, pharmacokinetics and pharmacodynamics of TQ-A3334, an oral toll-like receptor 7 agonist in healthy individuals.
机构信息
Phase I Clinical Research Center, the First Hospital of Jilin University, Jilin, China.
Department of Hepatology, The First Hospital of Jilin University, Jilin, China.
出版信息
Expert Opin Investig Drugs. 2021 Mar;30(3):263-269. doi: 10.1080/13543784.2021.1873275. Epub 2021 Jan 13.
BACKGROUND & AIMS: TQ-A3334, a selective, oral toll-like receptor (TLR)-7 agonist, is being developed to treat chronic hepatitis B (CHB). This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TQ-A3334 in healthy participants.
RESEARCH DESIGN AND METHODS
The effects of a single-ascending dose of TQ-A3334 (0.2-1.8 mg) combined with food (1.2 mg) were evaluated in 48 healthy participants.
RESULTS
No serious adverse events or discontinuations occurred in the study. The most common adverse reactions were lymphocyte count decreased and headache, which were generally consistent with IFN-α exposure and the mechanism of action of a TLR7 agonist. TQ-A3334 was rapidly absorbed, with a time to maximum plasma concentration of 0.42-0.5 h. Systemic exposure (C and AUC) to TQ-A3334 increased with a slight saturation proportion to dose. Food reduced the exposure of TQ-A3334. The concentrations of MCP-1, , and were observed to be slightly dose-dependent, ranging from 1.0 to 1.8 mg TQ-A3334.
CONCLUSIONS
Oral doses of 0.2-1.8 mg appeared to be safe and tolerated. PD activity was seen at doses ranging from 1.0 to 1.8 mg, indicating its possible future use to treat CHB.
TRIAL REGISTRATION
The trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20182248).
背景与目的
TQ-A3334 是一种选择性的、口服的 Toll 样受体（TLR）-7 激动剂，目前正在开发用于治疗慢性乙型肝炎（CHB）。本研究评估了健康受试者中单剂量 TQ-A3334（0.2-1.8 mg）联合食物（1.2 mg）的安全性、药代动力学（PK）和药效学（PD）。
研究设计和方法
评估了 TQ-A3334 单剂量递增（0.2-1.8 mg）联合食物（1.2 mg）的影响，共有 48 名健康参与者参与了该研究。
结果
研究中未发生严重不良事件或停药。最常见的不良反应是淋巴细胞计数减少和头痛，这与 IFN-α 暴露和 TLR7 激动剂的作用机制一致。TQ-A3334 吸收迅速，达峰时间为 0.42-0.5 h。TQ-A3334 的全身暴露（C 和 AUC）随剂量略有饱和比例增加。食物降低了 TQ-A3334 的暴露量。观察到 MCP-1、IL-6 和 TNF-α 的浓度呈轻微的剂量依赖性，范围为 1.0-1.8 mg TQ-A3334。
结论
0.2-1.8 mg 的口服剂量似乎安全且可耐受。PD 活性在 1.0-1.8 mg 剂量范围内可见，表明其未来可能用于治疗 CHB。
试验注册
该试验在中国临床试验网站注册（http://www.chinadrugtrials.org.cn/index.html # CTR20182248）。
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