Absence of effect of telbivudine on cardiac repolarization: results of a thorough QT/QTc study in healthy participants.

The effect of telbivudine on cardiac repolarization was eva­ luated in healthy participants at clinical and suprathera­ peutic doses. Sixty­two participants were enrolled, stratified by sex, and randomized according to a crossover design among 4 treatment sequences: placebo, a single moxi­ floxacin 400­mg dose as positive calibrator, and telbivudine 600 and 1800 mg/d for 7 days. Intensive time­matched elec­ trocardiogram measurements and pharmacokinetic sam­ pling were performed at baseline and on day 7 over 24 hours. For telbivudine and moxifloxacin, time­matched, placebo­adjusted change from baseline in QT was calcu­ lated and corrected using Fridericia’s formula (QTcF). While moxifloxacin produced the expected significant changes in QTcF, none of the changes in QTcF for either doses of telbivudine exceeded 5 ms, and none of the associated upper 1­sided 95% confidence intervals (CI) exceeded the limit of 10 ms. There was no increase in QTcF with increasing plasma telbivudine. The suprathera­ peutic dose of telbivudine was well tolerated with a safety profile similar to the clinical dose despite a 3­fold increase in plasma exposure. This study therefore met the criteria for a negative thorough QT study. Telbivudine had no adverse effect on cardiac repolarization in healthy partici­ pants, even at supratherapeutic exposure, suggesting a broad safety margin.