At the end of the run-in period, the patients were assigned (1:1) to either the topiroxostat 160 mg/day group or the matching placebo group at the central

registration center. Topiroxostat (or matching placebo) was administered orally at an initial dose of 40 mg/day for 2 weeks, followed in a stepwise manner by increase of the dose to 80 mg/day for 4 weeks, 120 mg/day for 8 weeks, and 160 mg/day for 8 weeks. All agents which could potentially affect the serum urate level were discontinued during the study. Because of assessment of the incidence of gouty arthritis in the study, we did not permit colchicine prophylaxis ICG-001 during the study. When gouty arthritis occurred during the study, colchicine, NSAIDs, or corticosteroids were used to treat the gouty arthritis at the investigator’s

discretion. Using antihypertensive agents and antihyperlipidemic agents were restricted during the study. The dose Selleck Proteasome inhibitor and type of these drugs were maintained as far as possible after randomization. To maintain the double-blind condition, serum urate levels measured after administration of the study drug in each patient were concealed from both the investigators and the patients throughout the study period. Endpoints The primary endpoints were the percent change of the serum urate level from the baseline to the final visit and change of the eGFR from the baseline to the final visit. The secondary efficacy endpoints were the percent change of the ACR from the not baseline to the final visit, changes in the home blood pressure from baseline to the final visit, proportion of patients with serum urate levels ≤356.88 μmol/L at the final visit, and change of the serum adiponectin level from baseline to the final visit. The ACR was calculated from the levels of albumin and creatinine in the urine sample taken at hospital. The safety and tolerability of study drug treatment were assessed by physical examinations, vital signs measurements, laboratory tests, and adverse

event (AE) monitoring. All laboratory tests were performed at a centralized lab. UA-767PC (A&D Company, Limited, Tokyo, Japan) was used for measurements of the home blood pressure values. Statistical methods We referred to the result of intervention study of Adavosertib concentration allopurinol for information about the sample size of this study [10]. We calculated that 53 patients per group were needed to detect an absolute difference in the serum creatinine level of 26.52 ± 41.5 μmol/L from the baseline to the final measurement between the topiroxostat group and placebo group at a two-sided significance level of 0.05, with at least 90 % power. Taking into consideration possible dropout of some patients, we set the required number of patients in each group at 60.