Yanwei Lin1, Xiaoxiang Chen1, Huihua Ding1, Ping Ye1, Jieruo Gu2, Xiaoxia Wang3, Zhenyu Jiang4, Detian Li5, Zhongming Wang6, Wubin Long7, Zhijun Li8, Gengru Jiang9, Xiaomei Li10, Liqi Bi11, Lindi Jiang12, Jian Wu13, Lian Guo14, Xiaoyan Cai15, Xin Lu16, Qinkai Chen17, Hong Chen18, Ai Peng19, Xiaoxia Zuo20, Rui Ning21, Zhe Zhang21, Yanfei Tai21, Tao Zhang21, Chunde Bao1. 1. Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai. 2. The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou. 3. Second Hospital of Shanxi Medical University, Taiyuan. 4. The First Bethune Hospital of Jilin University, Changchun. 5. Shengjing Hospital of China Medical University, Shenyang. 6. West China Hospital, Sichuan University. 7. Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu. 8. The First Affiliated Hospital of Bengbu Medical College, Bengbu. 9. Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai. 10. The First Affiliated Hospital of USTC Anhui Provincial Hospital, Hefei. 11. China-Japan Union Hospital of Jilin University, Changchun. 12. Zhongshan Hospital Affiliated to Fudan University, Shanghai. 13. The First Affiliated Hospital of SooChow University, Suzhou. 14. Chongqing Sanxia Central Hospital, Wanzhou. 15. Guangzhou First People's Hospital, Guangzhou. 16. China-Japan Friendship Hospital, Beijing. 17. The First Affiliated Hospital of Nanchang University, Nanchang. 18. The First Affiliated Hospital of Hainan Medical College, Haikou. 19. Shanghai Tenth People's Hospital, Shanghai. 20. Xiangya Hospital Central South University, Changsha. 21. Jiangsu Hengrui Medicine Co., Ltd, Shanghai, China.
Abstract
OBJECTIVE: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.
OBJECTIVE: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.
Authors: Christopher Jenkins; Jennifer H Hwang; Jeffrey B Kopp; Cheryl A Winkler; Sung Kweon Cho Journal: Front Pharmacol Date: 2022-08-23 Impact factor: 5.988