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QT/QTc study conducted in Japanese adult healthy subjects: A novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation
Author(s) -
Sugiyama Atsushi,
Hashimoto Hiroya,
Nakamura Yuji,
Fujita Tomoe,
Kumagai Yuji
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.226
Subject(s) - moxifloxacin , qt interval , medicine , placebo , anesthesia , xanthine oxidase inhibitor , crossover study , cardiology , pharmacology , xanthine oxidase , chemistry , biochemistry , alternative medicine , pathology , enzyme , antibiotics
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 180 mg), moxifloxacin (400 mg) or placebo in a single‐center, double‐blind, four‐period crossover design. Fridericia's formula (QTcF = QT/RR 0.33 ) 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 13.6 milliseconds with 90% confidence interval (CI) of 11.2 and 15.9 milliseconds at 4 hours post‐dose. The mean QTcF was hardly affected by either dose of topiroxostat, of which largest time‐matched difference from placebo administration was 2.9 milliseconds with 90% CI of 0.6 and 5.3 milliseconds at 4 hours post‐dose for 60 mg, and 2.3 milliseconds with 90% CI of 0 and 4.7 milliseconds at 1 hour post‐dose for 180 mg. 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.