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.

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 NCT02416167Keywords Hyperuricemia · Gout · Selective urate reabsorption inhibitor · URAT1 inhibitor · Dotinurad · FYU-981Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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

No abstract

Background There is no approved dosage and administration of inulin for children. Therefore, we measured inulin clearance (Cin) in pediatric patients with renal disease using the pediatric dosage and administration formulated by the Japanese Society for Pediatric Nephrology, and compared Cin with creatinine clearance (Ccr) measured at the same time. We examined to what degree Ccr overestimates Cin, using the clearance ratio (Ccr/Cin), and confirmed the safety of inulin in pediatric patients. Methods Pediatric renal disease patients aged 18 years or younger were enrolled. Inulin (1.0 g/dL) was administered intravenously at a priming rate of 8 mL/kg/hr (max 300 mL/hr) for 30 min. Next, patients received inulin at a maintenance rate of 0.7 × eGFR mL/min/1.73 m2 × body surface area (max 100 mL/hr) for 120 min. With the time the maintenance rate was initiated as a starting point, blood was collected at 30 and 90 min, while urine was collected twice at 60-min intervals. The primary endpoint was the ratio of Ccr to Cin (Ccr/Cin). Results Inulin was administered to 60 pediatric patients with renal disease; 1 patient was discontinued and 59 completed. The primary endpoint, Ccr/Cin, was 1.78 ± 0.52 (mean ± standard deviation). Regarding safety, five adverse events were observed in four patients (6.7%); all were non-serious. No adverse reactions were observed in this study. Conclusions The results in this study on the dosage and administration of inulin showed that inulin can safely and accurately determine GFR in pediatric patients with renal disease. ClinicalTrials.gov identifier NCT03345316.