Clinical efficacy and safety of dotinurad, a novel selective urate reabsorption inhibitor, in Japanese hyperuricemic patients with or without gout: randomized, multicenter, double-blind, placebo-controlled, parallel-group, confirmatory phase 2 study

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

Abstract

Background: Dotinurad, a novel selective urate reabsorption inhibitor (SURI), reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1) for the treatment of hyperuricemia with or without gout. We confirmed the serum uric acid lowering effect and safety of dotinurad.

Methods: This was a confirmatory, 12-week, randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose escalation, late phase 2 study. The study arms were dotinurad 0.5, 1, 2, or 4 mg and placebo. The primary endpoint was the percent change in serum uric acid level from the baseline to the final visit. The secondary endpoint was the percentage of patients achieving a serum uric acid level ≤ 6.0 mg/dL at the final visit.

Results: The study drugs were administered to 200 Japanese hyperuricemic patients with or without gout. The mean percent change in serum uric acid level from the baseline to the final visit in the dotinurad 0.5, 1, 2, and 4 mg groups and the placebo group was 21.81%, 33.77%, 42.66%, 61.09%, and - 2.83%, respectively. The percentage of patients achieving a serum uric acid level ≤ 6.0 mg/dL at the final visit in each group was 23.1%, 65.9%, 74.4%, 100%, and none, respectively. Regarding safety, the incidence of adverse events did not increase with dose escalation in the dotinurad groups. No significant differences were observed in the incidence of gouty arthritis in each group.

Conclusion: The serum uric acid lowering effect and safety of dotinurad were confirmed in hyperuricemic patients with or without gout. CLINICALTRIALS.

Gov identifier: NCT02416167.

Keywords: Dotinurad; FYU-981; Gout; Hyperuricemia; Selective urate reabsorption inhibitor; URAT1 inhibitor.

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 antihyperuricemic drugs or treatment affecting the serum uric acid level were subjected to the washout 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. Error bar indicates standard deviation

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