T Hosoya1, T Sasaki2, H Hashimoto3, R Sakamoto3, T Ohashi2. 1. Department of Pathophysiology and Therapy in Chronic Kidney Disease, Jikei University School of Medicine, Tokyo, Japan. 2. Medical R&D Division, Fuji Yakuhin Co., Ltd., Saitama, Japan. 3. Drug Development Center, Sanwa Kagaku Kenkyusho Co., Ltd., Aichi, Japan.
Abstract
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.
RCT Entities:
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 hyperuricemicpatients including gout. METHODS: We conducted an exploratory, phase 2a, multicentre, randomized, double-blind, 8-week, placebo-controlled study in Japanese hyperuricemicpatients 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 malepatients with or without gout. Further clinical studies aimed at evaluating the long-term safety and clinical efficacy are warranted.
Authors: Yoojin Lee; Jennifer Hwang; Shaan H Desai; Xiaobai Li; Christopher Jenkins; Jeffrey B Kopp; Cheryl A Winkler; Sung Kweon Cho Journal: J Clin Med Date: 2022-04-27 Impact factor: 4.964
Authors: Christopher Jenkins; Jennifer H Hwang; Jeffrey B Kopp; Cheryl A Winkler; Sung Kweon Cho Journal: Front Pharmacol Date: 2022-08-23 Impact factor: 5.988