PMID- 27079434
OWN - NLM
STAT- MEDLINE
DCOM- 20170410
LR  - 20171116
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Linking)
VI  - 41
IP  - 3
DP  - 2016 Jun
TI  - 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.
PG  - 298-305
LID - 10.1111/jcpt.12392 [doi]
AB  - 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.
CI  - (c) 2016 The Authors. Journal of Clinical Pharmacy and Therapeutics Published by 
      John Wiley & Sons Ltd.
FAU - Hosoya, T
AU  - Hosoya T
AD  - Department of Pathophysiology and Therapy in Chronic Kidney Disease, Jikei 
      University School of Medicine, Tokyo, Japan.
FAU - Sasaki, T
AU  - Sasaki T
AD  - Medical R&D Division, Fuji Yakuhin Co., Ltd., Saitama, Japan.
FAU - Hashimoto, H
AU  - Hashimoto H
AD  - Drug Development Center, Sanwa Kagaku Kenkyusho Co., Ltd., Aichi, Japan.
FAU - Sakamoto, R
AU  - Sakamoto R
AD  - Drug Development Center, Sanwa Kagaku Kenkyusho Co., Ltd., Aichi, Japan.
FAU - Ohashi, T
AU  - Ohashi T
AD  - Medical R&D Division, Fuji Yakuhin Co., Ltd., Saitama, Japan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160415
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Gout Suppressants)
RN  - 0 (Nitriles)
RN  - 0 (Pyridines)
RN  - 0J877412JV (FYX-051)
RN  - 268B43MJ25 (Uric Acid)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
SB  - IM
MH  - Adult
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Follow-Up Studies
MH  - Gout/*drug therapy
MH  - Gout Suppressants/*administration & dosage/adverse effects/therapeutic use
MH  - Humans
MH  - Hyperuricemia/*drug therapy
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Nitriles/*administration & dosage/adverse effects/therapeutic use
MH  - Pyridines/*administration & dosage/adverse effects/therapeutic use
MH  - Treatment Outcome
MH  - Uric Acid/blood
MH  - Xanthine Oxidase/antagonists & inhibitors
OTO - NOTNLM
OT  - gout
OT  - hyperuricemia
OT  - topiroxostat
EDAT- 2016/04/16 06:00
MHDA- 2017/04/11 06:00
CRDT- 2016/04/16 06:00
PHST- 2015/10/22 00:00 [received]
PHST- 2016/03/24 00:00 [accepted]
PHST- 2016/04/16 06:00 [entrez]
PHST- 2016/04/16 06:00 [pubmed]
PHST- 2017/04/11 06:00 [medline]
AID - 10.1111/jcpt.12392 [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2016 Jun;41(3):298-305. doi: 10.1111/jcpt.12392. Epub 2016 Apr 
      15.