title: Clinical efficacy and safety of topiroxostat in Japanese male hyperuricemic patients with or without gout: an exploratory, phase 2a, multicentre, randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  In Japan, although topiroxostat, a selective xanthine oxidoreductase inhibitor, has been used for the treatment of patients with hyperuricemia including gout, no published randomized controlled studies evaluating the dose-dependent relationship with respect to the serum urate-lowering efficacy have been reported. The aim of this study was to evaluate the dose-dependent relationship with serum urate-lowering efficacy and safety of topiroxostat in Japanese hyperuricemic patients including gout.
  
  
  METHODS
  We conducted an exploratory, phase 2a, multicentre, randomized, double-blind, 8-week, placebo-controlled study in Japanese hyperuricemic patients with or without gout. The study arms were placebo and topiroxostat 40, 60, 80 or 120 mg/day. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit.
  
  
  CONCLUSIONS
  One hundred and eighty-seven eligible patients were randomized and 186 received at least one dose of the study drug. The study results demonstrated a dose-dependent serum urate reduction effect ranging from 40 to 120 mg/day (P < 0·001, Jonckheere-Terpstra test). The mean per cent change in serum urate level from baseline at the final visit was -30·8% in the 120-mg group and 1·6% with placebo, with a between-group difference of -32·4% ([95% confidence interval, -38·9% to -25·9%]; P < 0·001). Incidences of overall adverse events (AEs) in the topiroxostat groups were comparable to those in the placebo group; however, the incidence of AEs in the 120-mg group was statistically lower than that in the placebo group. The incidences of gouty arthritis were not statistically but numerically higher in the topiroxostat 80- and 120-mg groups.
  
  
  CONCLUSIONS
  A dose-dependent serum urate-lowering efficacy of topiroxostat was observed in Japanese hyperuricemic male patients with or without gout. Further clinical studies aimed at evaluating the long-term safety and clinical efficacy are warranted.
authors.affiliation: Department of Pathophysiology and Therapy in Chronic Kidney Disease, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hosoya
authors.affiliation: Medical R&D Division, Fuji Yakuhin Co., Ltd., Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Drug Development Center, Sanwa Kagaku Kenkyusho Co., Ltd., Aichi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Drug Development Center, Sanwa Kagaku Kenkyusho Co., Ltd., Aichi, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Sakamoto
authors.affiliation: Medical R&D Division, Fuji Yakuhin Co., Ltd., Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohashi
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006073:Gout / Q000188:drug therapy*; D006074:Gout Suppressants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D006074:Gout Suppressants; D009570:Nitriles; D011725:Pyridines; C504882:FYX-051; D014527:Uric Acid; D014969:Xanthine Oxidase
keywords: gout; hyperuricemia; topiroxostat