NEW ORLEANS, LA— Supratherapeutic plasma levels of dabigatran etexilate do not prolong QTc intervals of the electrocardiogram (ECG), as reported from a study presented at ACC.11, the American College of Cardiology’s 60th Annual Scientific Session.
Arne Ring from Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany, and colleagues conducted the randomized, placebo-controlled, blinded, four-period crossover study, which had an open-label positive control (moxifloxacin 400mg) and assessed electrophysiological effects of single doses of dabigatran etexilate 150mg and 600mg in healthy subjects. ECG profiles using 12-lead 10-s ECGs were recorded at baseline and following the randomized study treatment in each period. The primary parameter was the time-matched change from baseline (TMCB) of the individually heart rate corrected QT interval (QTcI).
A total of 40 Caucasian subjects (20 male and 20 female) with a mean age of 39 years entered and completed the study. Mean values of the placebo-adjusted TMCB of QTcI for dabigatran etexilate were close to zero at all time points, and all 90% confidence intervals were between -5ms and 5ms (see Figure), well below the noninferiority margin of 10ms in the ICH E14 guidelines (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use).
Assay sensitivity was shown by placebo-adjusted TMCB of QTcI of >10ms at all time points between 1 and 6 hours following moxifloxacin administration. See Figure. The gMean Cmax of 88ng/mL (150mg) and 383ng/mL (600mg) in this QT study is considered to provide adequate exposure for the assessment of potential effects of dabigatran on the QT interval.