Open-label study of long-term administration of dotinurad in Japanese hyperuricemic patients with or without gout

Tatsuo Hosoya, Masahiko Fushimi, Daisuke Okui, Tomomitsu Sasaki, Tetsuo Ohashi, Tatsuo Hosoya, Masahiko Fushimi, Daisuke Okui, Tomomitsu Sasaki, Tetsuo Ohashi

Abstract

Background: Dotinurad is a novel selective urate reabsorption inhibitor (SURI) which reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1). This study was intended to verify the efficacy and safety of dotinurad following treatment for 34 or 58 weeks in hyperuricemic patients with or without gout.

Methods: This long-term study had an open-label design with dose escalation. The dose of dotinurad started at 0.5 mg/day and was increased progressively to 2 mg/day. If the serum uric acid level of patients did not reach ≤ 6 mg/dL at week 14, the dose was increased to 4 mg/day. The primary endpoint was the percent change in serum uric acid level from the baseline to each visit.

Results: At a dose of 2 mg, serum uric acid levels at week 34 and 58 were reduced from the baseline by 46.73% and 47.17%, respectively; at 4 mg, the respective values were 54.92% and 57.35%. At week 34 and 58, the percentages of patients achieving a serum uric acid levels ≤ 6.0 mg/dL with 2-mg dose were 89.11% and 91.30%, respectively; with 4 mg, the respective rates were 97.50% and 100.00%. In addition, the incidences of adverse events and adverse drug reactions were 65.2% and 21.8%, respectively.

Conclusion: Dotinurad at doses of 2-4-mg sufficiently reduced serum uric acid levels in hyperuricemic patients with or without gout, and its efficacy and safety were verified for long-term administration. ClinicalTrials.gov Identifier: NCT03006445.

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 uric acid lowering drugs or treatment affecting the serum uric acid level were subjected to the wash-out period. b When a patient failed to achieve a serum uric acid ≤ 6.0 mg/dL at week 14, the dose was increased to 4 mg after week 18
Fig. 2
Fig. 2
Flow diagram of patients in this study
Fig. 3
Fig. 3
Percent change in serum uric acid levels from the baseline to each visit. Error bars indicates standard deviation.*P < 0.05
Fig. 4
Fig. 4
Percentage of patients achieving a serum uric acid level ≤ 6.0 mg/dL at each visit. Error bars indicates standard deviation
Fig. 5
Fig. 5
Changes in serum uric acid level in response to follow treatment with dotinurad. Error bars indicates standard deviation.*P < 0.05

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