Huang Kai, Ding Ying, Que Linling, Chu Nannan, Shi Yunfei, Qian Zhenzhong, Qin Wei, Chen Yuanxin, Gu Xianghong, Wang Jiakun, Zhang Zhiwei, Xu Jianguo, He Qing
Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Wuxi Fuxin Pharmaceutical Research and Development Co, Ltd, Wuxi, China.
Front Pharmacol. 2022 Nov 4;13:1057949. doi: 10.3389/fphar.2022.1057949. eCollection 2022.
This study was conducted to investigate the safety, tolerability and pharmacokinetics (PK) of WXFL10203614 after single and multiple oral doses in healthy Chinese subjects. A single-center, randomized, double-blind, placebo-controlled phase Ⅰ study was performed on healthy Chinese subjects. In the single-dose study, Subjects were randomized into 7 dose levels of WXFL10203614 (1 mg group, = 2; 2, 5, 10, 17, 25 and 33 mg groups with placebo, 8 subjects per group, 2 of them given placebo). In the multiple-dose study, subjects received 5 or 10 mg WXFL10203614 once daily (QD), 5 mg twice daily (BID) or placebo for 7 consecutive days. Safety, tolerability and PK of WXFL10203614 were all assessed. A total of 592 subjects were screened, 50 subjects were enrolled in the single-dose study and 30 in the multiple-dose study. All adverse events (AEs) were mild or moderate and resolved spontaneously. No Serious Adverse Events (SAEs) or deaths were reported during the study. WXFL10203614 was absorbed rapidly after dosing with T of 0.48-0.98 h, C, AUC and AUC were all increased in a dose-related manner over the range of 1-33 mg. Renal excretion was the major route of elimination of WXFL10203614. Steady-state PK parameters (C, AUC and AUC) were elevated after once-daily administration of 5-10 mg WXFL10203614 and non- and weak drug accumulations were observed, whereas moderate drug accumulation occurred in the 5 mg BID group. WXFL10203614 exhibited good safety, tolerability and favorable PK profiles in healthy Chinese subjects, supporting further clinical development in patients with rheumatoid arthritis. http://www.chinadrugtrials.org.cn/index.html, #CTR20190069 and CTR20200143.
本研究旨在调查WXFL10203614在健康中国受试者单次及多次口服给药后的安全性、耐受性和药代动力学（PK）。对健康中国受试者进行了一项单中心、随机、双盲、安慰剂对照的Ⅰ期研究。在单剂量研究中，受试者被随机分为7个WXFL10203614剂量组（1mg组，n = 2；2、5、10、17、25和33mg组，每组8名受试者，其中2名给予安慰剂）。在多剂量研究中，受试者连续7天每天一次（QD）接受5或10mg WXFL10203614、每天两次（BID）接受5mg或接受安慰剂。对WXFL10203614的安全性、耐受性和PK进行了评估。共筛选了592名受试者，50名受试者纳入单剂量研究，30名受试者纳入多剂量研究。所有不良事件（AE）均为轻度或中度，且自行缓解。研究期间未报告严重不良事件（SAE）或死亡。WXFL10203614给药后吸收迅速，达峰时间（Tmax）为0.48 - 0.98小时，在1 - 33mg范围内，峰浓度（Cmax）、血药浓度-时间曲线下面积（AUC）和AUC均呈剂量相关增加。肾脏排泄是WXFL10203614的主要消除途径。每天一次给予5 - 10mg WXFL10203614后，稳态PK参数（Cmax、AUC和AUC）升高，未观察到药物蓄积和轻度药物蓄积，而5mg BID组出现中度药物蓄积。WXFL10203614在健康中国受试者中表现出良好的安全性、耐受性和良好的PK特征，支持在类风湿性关节炎患者中进一步开展临床研究。http://www.chinadrugtrials.org.cn/index.html, #CTR20190069和CTR20200143
