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. (15th April 2016)

• Record Type: Journal Article
• Authors: Hosoya, T.; Sasaki, T.; Hashimoto, H.; Sakamoto, R.; Ohashi, T.
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 41:Number 3(2016:Jun.)
• Page Start: 298
• Page End: 305
• Publication Date: 2016-04-15
• Subjects: gout -- hyperuricemia -- topiroxostat; Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.12392
• Languages: English
• ISSNs: 0269-4727

Abstract

Summary: What is known and 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. Results and discussion: 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. What is new and 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. Abstract : We evaluated the dose–response relationship in respect of the serum urate‐lowering efficacy of topiroxostat, a novel selective xanthine oxidoreductase inhibitor for the treatment of hyperuricemia with or without gout in Japan, which was newly developed by Fuji Yakuhin Co., Ltd. The study demonstrated its dose–response relationship in respect of the serum urate reduction and a superior mean per cent change of the serum urate from the baseline at the end of the study period.