Evaluation of Assay Sensitivity and the Concentration-Effect Relationship of Moxifloxacin in a QT/QTc Study in Japan.

ABSTRACT

To investigate the potential for a QT/QTc study in Japan, a randomized, single-blind, crossover study was conducted using moxifloxacin in 64 healthy Japanese male volunteers. A 12-lead Holter electrocardiogram was used to test a relatively small population at each of 4 incorporated clinical research units to confirm the assay sensitivity and efficiency. Moxifloxacin (400 mg) significantly prolonged QT intervals, as previously reported, with small variations in this study. In addition, the placebo-adjusted mean QTcF changes from predose baseline showed that the lower bounds of the 1-sided 95% confidence interval exceeded 5 milliseconds at all of the clinical research units. The data also indicated statistically significant concentration-QT relationships in 3 of the 4 research units by separate analysis. These findings and the small amount of variability in this study suggest the feasibility of conducting a high-quality QT/QTc study in Japan.