QT/QTc Study Conducted in Japanese Adult Healthy Subjects: A Novel Xanthine Oxidase Inhibitor Topiroxostat Was Not Associated With QT Prolongation

A QT/QTc study was conducted in compliance with ICH E14 guideline to evaluate the effects of a new xanthine oxidase inhibitor topiroxostat in Japanese healthy subjects. Forty-eight Japanese healthy subjects (males 24; females 24) received a single oral dose of topiroxostat (60 or 180mg), moxifloxacin (400mg) or placebo in a single-center, double-blind, four-period crossover design. Fridericia's formula (QTcF=QT/RR0.33) was used as a primary method for QT-interval correction. The mean QTcF was prolonged by moxifloxacin, of which largest time-matched difference from placebo administration was 13.6milliseconds with 90% confidence interval (CI) of 11.2 and 15.9milliseconds at 4hours post-dose. The mean QTcF was hardly affected by either dose of topiroxostat, of which largest time-matched difference from placebo administration was 2.9milliseconds with 90% CI of 0.6 and 5.3milliseconds at 4hours post-dose for 60mg, and 2.3milliseconds with 90% CI of 0 and 4.7milliseconds at 1hour post-dose for 180mg. The results were essentially the same in the sex subgroup analysis. Moxifloxacin can be used as a positive control for QT/QTc studies in Japanese subjects; and topiroxostat may not cause QT-interval prolongation in males as well as females.