The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.

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Background: The primary endpoint of a thorough QT study (TQTS) is the change from baseline in QT corrected (QTc) measured on electrocardiograms (ECG) tracings. It has been suggested that during a crossover study, the time-matched or predose baseline could be recorded. The choice of method for baseline ECG collection may influence the results and the cost of the TQTS. Objective: The objective of our study was to compare the collection of a time-matched baseline before each period (TM EACH), an average of all the time-matched baseline (TM MEAN), a time-matched baseline before period 1 (TM P1) and a predose baseline (PD EACH) on QT interval prolongation induced by moxifloxacin, in a 30 subjects, 5 arm cross-over TQTS. Results: Moxifloxacin induced a similar significant increase in QT corrected using Fridericia's formula (QTc) (lower limit of the confidence interval excluded 5 ms) at all time-points between 0.5 hours and 12 hours with all baseline methods. TM EACH was associated with a lower within subject variability (SD 5.59 ms) than TM MEAN and TM P1 (5.90 and 6.90 ms, respectively). PD EACH was associated with the highest variability (7.41 ms). Conclusion: The collection of ECG tracings during a full baseline day before each period was associated with the lowest variability. However, the two more cost effective designs (TM P1 and PD EACH) were sufficient, in this small TQTS, to significantly detect moxifloxacin.