Abstract
The purpose of this study was to measure the electrocardiographic (ECG) effects of WCK 2349 (the L-alanine ester prodrug of levonadifloxacin) at a supratherapeutic oral dose of 2,600 mg. A total of 48 healthy volunteers were randomized to treatment with placebo, WCK 2349, or oral moxifloxacin, 400 mg, in a crossover-designed thorough QT study. A supratherapeutic mean maximum levonadifloxacin concentration (C(max) ) of 43.3 μg/mL was achieved at 3.1 hours. A therapeutic dose of 1,000 mg b.i.d. in a previous study in patients resulted in a C(max) of 17.8 μg/mL. WCK 2349 exerted no significant effect on baseline- and placebo-corrected QTcF (QT interval corrected for heart rate (HR) by the Fridericia formula), QRS, or PR interval. HR was transiently accelerated by a maximum of 14.4 (95% confidence interval, 11.80-16.92) beats per minute (bpm) at 3 hours. Concentration-effect modeling predicted a mean increase of 8.0 bpm at C(max) at the standard therapeutic dose. A therapeutic dose of 1,000 mg b.i.d. of WCK 2349 is not expected to cause clinically significant ECG effects, except for a possible transient increase in HR, which seems to be clinically insignificant.