Background Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by selective inhibition of the urate transporter 1. We evaluated the efficacy and safety of dotinurad versus febuxostat, a widely used drug in Japan, in hyperuricemic Japanese patients with or without gout. Methods This was a multicenter, randomized, double-blind, active-controlled, parallel-group, forced-titration study in hyperuricemic patients. Study treatment in the dotinurad and febuxostat groups was initiated at 0.5 and 10 mg/day, followed by dose titration to 2 and 40 mg/day, respectively, over 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 203 hyperuricemic patients with or without gout were enrolled in the study and randomized to receive dotinurad or febuxostat. The percent change in serum uric acid level from the baseline to the final visit was 41.82% in the dotinurad group and 44.00% in the febuxostat group. The mean difference was − 2.17% (two-sided 95% confidence interval − 5.26% to 0.92%). The lower limit of the interval was above the non-inferiority margin (− 10%), demonstrating the noninferiority of dotinurad to febuxostat. The profiles of adverse events and adverse drug reactions raised no noteworthy safety concerns in either group. Conclusion The non-inferiority of dotinurad to febuxostat in terms of serum uric acid lowering effect was confirmed. No noteworthy safety concerns arose.

Aim To investigate the safety and efficacy of dienogest (DNG), a progestational 19‐norsteroid, administered for 52 weeks in patients with primary and secondary dysmenorrhea. Methods A total of 147 patients with dysmenorrhea received 1 mg of DNG orally each day for 52 weeks. The dose could be increased to 2 mg/day at or after Week 12 according to the investigator's determination. The primary safety endpoint was evaluation of adverse events, and the secondary safety endpoint was evaluation of adverse drug reactions. The number of days and severity of genital bleeding were assessed according to records in the patients' diary. Lower abdominal pain and/or low back pain because of dysmenorrhea were assessed according to the dysmenorrhea score. Results The most frequent adverse drug reaction was irregular uterine bleeding (94.6%). Most subjects completed the 52‐week administration. Genital bleeding was more likely to occur in subjects with secondary dysmenorrhea than in those with primary dysmenorrhea, and in subjects with “uterine myoma or adenomyosis” than in those with “endometriosis alone.” In any of the categorizations, there tended to be fewer days with genital bleeding as the treatment period increased in length, and most of the genital bleeding cases were mild. The change from baseline in the dysmenorrhea score (mean ± standard deviation [SD]) was −3.7 ± 1.6 at Week 24 of treatment and −4.0 ± 1.3 at Week 52. Conclusion This study showed favorable tolerability of the long‐term use of DNG to patients with dysmenorrhea and a sustainable pain relief effect.

Objective: To evaluate the efficacy, safety, and clinically recommended dose of dienogest (DNG; 0.5 mg/d, 1 mg/d, and 2 mg/d) in the treatment of primary dysmenorrhea. Design: A phase II, randomized, double-blind, multicenter, placebo-controlled study. Setting: Twenty study sites. Patients: A total of 235 patients with primary dysmenorrhea. Intervention(s): Patients were randomized to receive orally a placebo, DNG (0.5 mg/d, 1 mg/d, or 2 mg/d) or ethinylestradiol 0.02 mg/ drospirenone 3 mg (an open-label reference drug) for 12 weeks. Main Outcome Measure(s): The primary endpoint was the change from baseline in the dysmenorrhea score at week 12 of treatment. The secondary endpoint was the change from baseline in the visual analogue scale at week 12 of treatment. Subjects were assessed for lower abdominal pain and/or low back pain. Results: All DNG arms were superior to the placebo arm in terms of the change from baseline in the dysmenorrhea score. The results suggest an equal or greater effect of DNG 1 and 2 mg/d in relieving pain, when compared to the reference drug. In the safety profile of DNG, including irregular uterine bleeding, there was no obvious difference among the doses of DNG. A significant decrease in the serum estradiol concentration compared to that in the placebo arm was not observed in the DNG 1 mg/d arm but was observed in the DNG 2 mg/d arm. Conclusion(s):The results suggest that DNG at a dose of 1 mg/d is an effective and well-tolerated treatment for primary dysmenorrhea.

Background Dotinurad is a novel, selective urate reabsorption inhibitor (SURI), which reduces serum uric acid levels by selective inhibition of the urate transporter 1 (URAT1). The Japanese guideline for the management of hyperuricemia and gout recommends that drug selection should be based on classification of hyperuricemia as a fundamental principle. However, there may be some cases where this principle is not observed. We investigated the pharmacodynamics and safety of dotinurad in outpatients with uric acid overproduction or uric acid underexcretion type. Methods This was a multicenter, open-label, forced titration study. Patients were classified as uric acid overproduction or underexcretion type. Study treatment was initiated at 0.5 mg/day, followed by dose titration to the estimated maximum dose of 4 mg/day over 14 weeks. The primary endpoint was urinary uric acid excretion at each 24-h urine collection. Results A total of 26 hyperuricemic patients with or without gout were enrolled in the study and assigned to the uric acid overproduction group (overproduction group) or the uric acid underexcretion group (underexcretion group). Although urinary uric acid excretion, the primary endpoint, tended to be slightly greater in the overproduction group, no notable difference was noted between the two hyperuricemic types. Neither type had noteworthy safety concerns associated with dotinurad. ConclusionThe results of the study demonstrated no relevant differences between the hyperuricemic types in terms of pharmacodynamic action and safety of dotinurad.Keywords Hyperuricemia · Gout · Selective urate reabsorption inhibitor (SURI) · URAT1 inhibitor · Dotinurad · FYU-981 Dotinurad: Novel URAT1 inhibitorElectronic supplementary material The online version of this article (https ://doi. S104Clinical and Experimental Nephrology (2020) 24 (Suppl 1):S103-S111

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