POS0255 A RANDOMIZED, MULTICENTER, DOUBLE-BLIND, PHASE 3 STUDY COMPARING EFFICACY OF DOTINURAD AND FEBUXOSTAT FOR THE TREATMENT OF GOUT IN CHINESE SUBJECTS

Background:

Gout is increasingly common disease in China. Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by selective inhibition of the urate transporter 1. Dotinurad was approved for hyperuricemia and gout in Japan in 2020. Febuxostat is nonpurine xanthine oxidase inhibitor, a widely used urate lowering drug in clinical practice in China. This was a Phase 3 study to evaluate the efficacy and safety of dotinurad versus febuxostat in Chinese gout patients.

Objectives:

The study was to primarily confirm the superiority of dotinurad 4 mg to febuxostat 40 mg and evaluate the safety in Chinese subjects with gout, and was to secondarily confirm the non-inferiority of dotinurad 2 mg to febuxostat 40 mg.

Methods:

This is a multicenter, randomized, double-blind, active-controlled, parallel-group, Phase 3 study (NCT05007392). Gout subjects with serum uric acid (SUA) level >7.0 mg/dL were randomized into dotinurad or febuxostat group in a ratio of 1:1 and received dotinurad 1 mg/day for the first 4 weeks, 2 mg/day for 8 weeks, and 4 mg/day for 12 weeks; or febuxostat 20 mg/day for the first 4 weeks, and 40 mg/day for 20 weeks. The randomization was stratified by baseline SUA level category (<9; 9 to <10; 10 to <11; ≥11 mg/dL) and baseline body mass index (BMI) category (<25; ≥25 kg/m²). The primary endpoint is the proportion of subjects with ≤6.0 mg/dL in SUA level at Week 24 and the secondary endpoint is the proportion of subjects with ≤6.0 mg/dL in SUA level at Week 12. The prespecified non-inferiority margin was –10%, which was for the reference purpose only. For missing SUA values, data from the last available post-baseline assessment were used for the efficacy analysis.

Results:

A total of 451 gouty subjects were randomized in the study. Of these, 225 subjects were randomized to the dotinurad group and 226 subjects to the febuxostat group. Of these, 441 (220 in the dotinurad group, 221 in the febuxostat group) subjects were included in the Full Analysis Set (FAS). In the FAS, 433 (98.2%) subjects were male; the median age was 38.0 years (range: 18 to 72 years), 321 (72.8%) subjects had baseline BMI ≥ 25 (kg/m²); mean SUA at baseline was 9.66 (standard deviation [SD] 1.439) mg/dL. The mean time since diagnosis of gout was 5.34 (SD 5.459) years, and most subjects (95.9%) had previously experienced gouty arthritis. Baseline characters were well balanced between the groups. The study met its primary endpoint (the proportion of subjects with ≤6.0 mg/dL in SUA level at Week 24) with 73.6% (95% confidence interval [CI] 67.8-79.5) in the dotinurad group and 38.1% (95% CI 31.6-44.5) in the febuxostat group. Dotinurad 4mg demonstrated superiority to febuxostat 40mg with a treatment difference of 35.87% (95% CI 27.36-44.37, p<0.001). Dotinurad 2mg showed the non-inferiority to febuxostat 40mg (55.5% vs 50.5%, respectively, difference of proportion: 5.24% [95% CI: –3.69, 14.17]). The most frequent treatment-emergent adverse events were gouty arthritis (43.5%), COVID-19 (25.6%) and hepatic function abnormal (10.8%) in the dotinurad group and gouty arthritis (34.7%), COVID-19 (25.3%) and alanine aminotransferase increased (12.4%) in the febuxostat group. Safety profile was generally similar and there were no noteworthy safety concerns in either group.

Conclusion:

Dotinurad 4 mg demonstrated superiority to febuxostat 40 mg in lowering SUA and dotinurad 2 mg was non-inferior to febuxostat 40mg in Chinese subjects with gout. Dotinurad was well tolerated.

REFERENCES:

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Acknowledgements:

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Disclosure of Interests:

Zhuoli Zhang: None declared, Jia Sun: None declared, Yu Wang: None declared, Xuan Zhang: None declared, Dongmei Guo: None declared, Jiankang Hu: None declared, Dongzhou Liu: None declared, Zhengnan Gao: None declared, Changgui LI: None declared, Yibing Lu: None declared, Xiaodan Kong: None declared, Yu Liu: None declared, Zhenyu Jiang: None declared, Bin Yi: None declared, Hongfeng Zhang: None declared, Baijie Xu: None declared, Shihao Yu Eisai China Inc., Rieko Kokan Eisai Co. Ltd., Eisai Co. Ltd., Kohei Ishikawa Eisai Co. Ltd., Eisai Co. Ltd., Mikiko Kawakatsu Eisai Co. Ltd., Eisai Co. Ltd.