Lin Yanwei, Chen Xiaoxiang, Ding Huihua, Ye Ping, Gu Jieruo, Wang Xiaoxia, Jiang Zhenyu, Li Detian, Wang Zhongming, Long Wubin, Li Zhijun, Jiang Gengru, Li Xiaomei, Bi Liqi, Jiang Lindi, Wu Jian, Guo Lian, Cai Xiaoyan, Lu Xin, Chen Qinkai, Chen Hong, Peng Ai, Zuo Xiaoxia, Ning Rui, Zhang Zhe, Tai Yanfei, Zhang Tao, Bao Chunde
Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai.
The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou.
Rheumatology (Oxford). 2021 Nov 3;60(11):5089-5097. doi: 10.1093/rheumatology/keab198.
To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia.
This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5.
99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P < 0.05 for 5 mg and 10 mg SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg SHR4640 and benzbromarone, respectively, vs placebo (5.9%; P < 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported.
The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia.
ClinicalTrials.gov number, NCT03185793.
评估高选择性尿酸转运蛋白1抑制剂SHR4640对中国高尿酸血症患者的疗效和安全性。
这是一项随机双盲剂量范围的II期研究。纳入血清尿酸（sUA）水平≥480µmol/l伴痛风、≥480µmol/l无痛风但有合并症或≥540µmol/l的受试者。受试者被随机分配（1:1:1:1:1），分别每日一次接受2.5mg、5mg、10mg的SHR4640、50mg的苯溴马隆或安慰剂。主要终点是在第5周达到目标sUA水平≤360µmol/l的受试者比例。
99.5%的受试者（n = 197）为男性，95.9%的受试者有痛风病史。在第5周达到目标sUA的受试者比例在5mg、10mg SHR4640和苯溴马隆组中分别为32.5%、72.5%和61.5%，显著高于安慰剂组（0%；5mg和10mg SHR4640组P < 0.05）。在第5周时，5mg、10mg SHR4640和苯溴马隆组的sUA分别降低了32.7%、46.8%和41.8%，而安慰剂组降低了5.9%（各比较P < 0.001）。所有组中需要干预的痛风发作发生率相似。所有组中治疗期间出现的不良事件（TEAE）发生率相当，且未报告严重TEAE。
本研究表明，与安慰剂相比，中国高尿酸血症患者每日一次服用5mg/10mg SHR4640进行5周治疗后，具有更好的降低sUA效果和良好的耐受性。
ClinicalTrials.gov编号，NCT03185793。
