scholarly journals Comparative study of a novel selective urate reabsorption inhibitor “dotinurad” among patient groups with different stages of renal dysfunction

2021 ◽  
Author(s):  
Toshinari Takahashi ◽  
Takanobu Beppu ◽  
Yuji Hidaka ◽  
Tatsuo Hosoya
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Renal Dysfunction ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Patient Groups ◽  
Urate Reabsorption

Abstract Background Dotinurad is a selective urate reabsorption inhibitor (SURI), which selectively inhibits URAT1 to lower serum uric acid levels in patients with hyperuricemia. Herein, the effects of dotinurad were compared among patient groups with different stages of renal dysfunction. Methods Patient data from four clinical trials were pooled and divided into four groups according to the stage of renal dysfunction to compare the effects of dotinurad at different stages. The grouping (stages G1–G3b) was based on the estimated glomerular filtration rate (eGFR) of the patients. In addition, patient data from a long-term study (34 or 58 weeks) were evaluated in the same manner. Results In the pooled analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 64.7–100.0% at a dose of 2 or 4 mg. In the long-term analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 60.0–100.0% at a dose of 2 or 4 mg. Although the outcomes in stage G3b were worse due to higher baseline serum uric acid levels, satisfactory outcomes were observed in all stages. Even in stages G3a and G3b, when renal function declined, the eGFR remained constant throughout the dose period. Conclusion The efficacy of dotinurad was confirmed in hyperuricemic patients with normal renal function (stage G1) and mild to moderate renal dysfunction (stage G2–G3b). Dotinurad was found to be effective in the treatment of hyperuricemia in patients with mild to moderate renal dysfunction.

scholarly journals Serum Uric Acid Level, Longitudinal Blood Pressure, Renal Function, and Long-Term Mortality in Treated Hypertensive Patients

Hypertension ◽  
2013 ◽  
Vol 62 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Jesse Dawson ◽  
Panniyammakal Jeemon ◽  
Lucy Hetherington ◽  
Caitlin Judd ◽  
Claire Hastie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Hypertensive Patients ◽  
Long Term Mortality

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

2019 ◽  
Vol 24 (S1) ◽  
pp. 80-91 ◽  
Author(s):  
Tatsuo Hosoya ◽  
Masahiko Fushimi ◽  
Daisuke Okui ◽  
Tomomitsu Sasaki ◽  
Tetsuo Ohashi
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Efficacy And Safety ◽  
Open Label ◽  
Long Term Study ◽  
Term Administration

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

scholarly journals The effect for hyperuricemia inpatient of uric acid overproduction type or in combination with topiroxostat on the pharmacokinetics, pharmacodynamics and safety of dotinurad, a selective urate reabsorption inhibitor

2019 ◽  
Vol 24 (S1) ◽  
pp. 92-102
Author(s):  
Daisuke Okui ◽  
Tomomitsu Sasaki ◽  
Masahiko Fushimi ◽  
Tetsuo Ohashi
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Combination Group ◽  
Acid Excretion ◽  
Uric Acid Excretion ◽  
Percent Change ◽  
Urate Reabsorption

Abstract Background Dotinurad, a novel selective urate reabsorption inhibitor (SURI), increases urinary uric acid excretion. The aim of this study is to examine the pharmacokinetics, pharmacodynamics, and safety of dotinurad according to the type of hyperuricemia, with or without concomitant use of xanthine oxidase inhibitor, in uric acid “overproduction type” patients. Methods This open-label clinical pharmacology study was conducted in a hospital. Dotinurad 1 mg was administered for 7 days to hyperuricemic patients with uric acid “overproduction type” (overproduction group, n = 6; and combination group, n = 6) and uric acid “underexcretion type” (underexcretion group, n = 6). In the combination group, topiroxostat 80 mg was used concomitantly. Results No significant differences were observed in pharmacokinetics and safety between overproduction group and underexcretion group, and the percent change in serum uric acid level and the amount of urinary uric acid excretion after administration were comparable. In “overproduction type” patients of combination group, the percent change in serum uric acid level significantly increased and the amount of urinary uric acid excretion significantly decreased compared to those of overproduction group. No clinically meaningful differences were observed in safety between the overproduction group and the combination group. Conclusion In inpatients, differences in hyperuricemic type did not significantly influence the pharmacokinetics, pharmacodynamics, and safety of dotinurad. Moreover, in “overproduction type”, the coadministration of dotinurad and topiroxostat had an add-on serum uric acid lowering effect and suppressed urinary uric acid excretion. Trial registration ClinicalTrials.gov Identifier: NCT02837198.

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

2019 ◽  
Vol 24 (S1) ◽  
pp. 44-52 ◽  
Author(s):  
Tatsuo Hosoya ◽  
Takafumi Sano ◽  
Tomomitsu Sasaki ◽  
Masahiko Fushimi ◽  
Tetsuo Ohashi
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Final Visit ◽  
Double Blind ◽  
Parallel Group ◽  
Phase 2 Study ◽  
Urate Reabsorption

Abstract Background Dotinurad, a novel selective urate reabsorption inhibitor (SURI) that has a future potential for the treatment of hyperuricemia, reduces serum uric acid levels by selectively inhibiting urate transporter 1 (URAT1). We evaluated the efficacy and safety of dotinurad in hyperuricemic Japanese patients with or without gout. Methods The study design was an exploratory, early phase 2 study that ran for 8 weeks. It was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, and performed in a dose escalation manner. There were four study arms consisting of dotinurad 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 A total of 80 hyperuricemic patients with or without gout were enrolled and randomly assigned to the dotinurad or placebo groups. The mean percent change in serum uric acid level from the baseline to the final visit in the dotinurad 1, 2, 4 mg, and placebo groups was 37.03%, 50.91%, 64.37%, and 0.85%, respectively. The percentages of patients achieving a serum uric acid level ≤ 6.0 mg/dL at the final visit in each group were 75.0%, 89.5%, 95.2%, and none, respectively. The incidence of adverse events was comparable among all groups. Conclusion Dotinurad has a substantial serum uric acid lowering effect in patients with hyperuricemia. No serious adverse event was found. ClinicalTrials.gov Identifier NCT02344862

scholarly journals 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

2019 ◽  
Vol 24 (S1) ◽  
pp. 53-61 ◽  
Author(s):  
Tatsuo Hosoya ◽  
Takafumi Sano ◽  
Tomomitsu Sasaki ◽  
Masahiko Fushimi ◽  
Tetsuo Ohashi
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Final Visit ◽  
Double Blind ◽  
Parallel Group ◽  
Phase 2 Study ◽  
Urate Reabsorption

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

U-shaped relationship between serum uric acid level and decline in renal function during a 10-year period in female subjects: BOREAS-CKD2

2020 ◽  
Vol 44 (1) ◽  
pp. 107-116 ◽  
Author(s):  
Kazuma Mori ◽  
Masato Furuhashi ◽  
Marenao Tanaka ◽  
Keita Numata ◽  
Takashi Hisasue ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Female Subjects
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