Dotinurad versus benzbromarone in Japanese hyperuricemic patient with or without gout: a randomized, double-blind, parallel-group, phase 3 study

Tatsuo Hosoya, Takafumi Sano, Tomomitsu Sasaki, Masahiko Fushimi, Tetsuo Ohashi, Tatsuo Hosoya, Takafumi Sano, Tomomitsu Sasaki, Masahiko Fushimi, Tetsuo Ohashi

Abstract

Background: Dotinurad is a novel selective urate reabsorption inhibitor that reduces serum urate levels in hyperuricemic patients with or without gout by selectively inhibiting urate transporter 1. This study was conducted to compare the efficacy and safety of dotinurad with those of benzbromarone.

Methods: In this 14-week, randomized, multicenter, double-blind, parallel-group, dose escalation, benzbromarone-controlled, phase 3 study, hyperuricemic patients with or without gout were randomized to two groups that received either dotinurad 2 mg or benzbromarone 50 mg. Dotinurad or benzbromarone was administered once a day for 14 weeks. The primary endpoint was the percent change in serum uric acid level from the baseline to the final visit.

Results: A total of 201 Japanese hyperuricemic patients with or without gout (dotinurad: 102, benzbromarone: 99) received at least one dose of the study drug. The mean percent change in serum uric acid level from the baseline to the final visit in the dotinurad and benzbromarone groups was 45.9% and 43.8%, respectively. Non-inferiority of dotinurad 2 mg to benzbromarone 50 mg in lowering serum uric acid was verified by the predefined non-inferiority margin (95% CI - 1.27 to 5.37%). The incidence of adverse events and adverse drug reactions was comparable between the two groups.

Conclusion: Dotinurad 2 mg was verified to have a non-inferior serum uric acid lowering effect compared with benzbromarone 50 mg, in Japanese hyperuricemic patients with or without gout. CLINICALTRIALS.

Gov identifier: NCT03100318.

Keywords: Benzbromarone; Dotinurad; FYU-981; Hyperuricemia; Selective urate reabsorption inhibitor; Uricosuric.

Conflict of interest statement

Fuji Yakuhin Co., Ltd. (Fuji) the manufacturer of dotinurad sponsored this study. TH was advisor to Fuji regarding this study and received consultant and manuscript fees. The other authors were employees of Fuji.

Figures

Fig. 1
Fig. 1
Dosing schedule. (a)Patients who had been treated with uric acid lowering drugs or treatment affecting the serum uric acid level were subjected to the wash-out period
Fig. 2
Fig. 2
Flow diagram of study protocol
Fig. 3
Fig. 3
Changes in serum uric acid level in response to follow treatment with dotinurad and benzbromarone. Error bars indicates standard deviation

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