Efficacy and Safety of Dotinurad Versus Febuxostat for the Treatment of Gout: A Randomized, Multicenter, Double-Blind, Phase 3 Trial in China

多替努拉与非布司他治疗痛风的疗效和安全性比较:一项在中国开展的随机、多中心、双盲3期临床试验

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Abstract

OBJECTIVE: Dotinurad is a selective urate reabsorption inhibitor that reduces serum urate levels. We compared the efficacy and safety of dotinurad with febuxostat in Chinese patients with gout. METHODS: This phase 3, multicenter, randomized, double-blind, parallel-group study randomly allocated (1:1) eligible patients with gout to receive oral dotinurad or febuxostat. The primary end point was the responder rate (proportion of patients achieving serum urate levels ≤6.0 mg/dL) at week 24 in the full analysis set (FAS) to demonstrate superiority of dotinurad 4 mg/day to febuxostat 40 mg/day. The secondary end points included the responder rate at week 12 to show the noninferiority of dotinurad 2 mg/day to febuxostat 40 mg/day. Treatment-emergent adverse events (TEAEs) were also recorded. RESULTS: A total of 451 patients were randomized, and 441 were included in the FAS. Baseline characteristics were well balanced between treatment groups. The responder rate at week 24 was significantly higher for dotinurad 4 mg/day versus febuxostat 40 mg/day (73.6% vs 38.1%; adjusted difference 35.9% [95% confidence interval (CI) 27.4%-44.4%]; P < 0.0001), and at week 12, dotinurad 2 mg/day was noninferior to febuxostat 40 mg/day (55.5% vs 50.5%; adjusted difference 5.2% [95% CI -3.7% to 14.2%]). Incidences of TEAEs in the dotinurad and febuxostat groups were similar. CONCLUSION: Dotinurad 4 mg/day was superior to febuxostat 40 mg/day in achieving serum urate levels ≤6.0 mg/dL at week 24 and was well tolerated in Chinese patients with gout.

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