Clinical Drug Investigation

, Volume 32, Issue 5, pp 339–351

Effects of Bilastine on T-wave Morphology and the QTc Interval

A Randomized, Double-Blind, Placebo-Controlled, Thorough QTc Study

Authors

    • Medical Informatics Group (MI), Department of Health Science and TechnologyAalborg University
  • Johannes J. Struijk
    • Medical Informatics Group (MI), Department of Health Science and TechnologyAalborg University
  • Jørgen K. Kanters
    • Department of Cardiology PGentofte University Hospital
    • Danish National Research Foundation, Centre for Cardiac Arrhythmia (DARC), Laboratory of Experimental CardiologyUniversity of Copenhagen
    • Department of Cardiology S, Aalborg HospitalAarhus University Hospitals
  • Mads P. Andersen
    • Center for Sensory Motor Interaction (SMI), Department of Health Science and TechnologyAalborg University
  • Egon Toft
    • Center for Sensory Motor Interaction (SMI), Department of Health Science and TechnologyAalborg University
  • Beno⩼ Tyl
    • Department of CardiologyRobert Ballanger’s Hospital
Original Research Article

DOI: 10.2165/11599270-000000000-00000

Cite this article as:
Graff, C., Struijk, J.J., Kanters, J.K. et al. Clin Drug Investig (2012) 32: 339. doi:10.2165/11599270-000000000-00000

Abstract

Background and Objectives: The International Conference of Harmonisation (ICH) E14 guideline for thorough QT studies requires assessing the propensity of new non-antiarrhythmic drugs to affect cardiac repolarization. The present study investigates whether a composite ECG measure of T-wave morphology (Morphology Combination Score [MCS]) can be used together with the heart rate corrected QT interval (QTc) in a fully ICH E14-compliant thorough QT study to exclude clinically relevant repolarization effects of bilastine, a novel antihistamine.

Methods: Thirty participants in this crossover study were randomly assigned to receive placebo, moxifloxacin 400 mg, bilastine at therapeutic and supratherapeutic doses (20 and 100 mg) and bilastine 20 mg co-administered with ketoconazole 400 mg. Resting ECGs recorded at 12 nominal time points before and after treatments were used to determine Fridericia corrected QTc (QTcF) and MCS from the T-wave characteristics: asymmetry, flatness and notching.

Results: There were no effects of bilastine monotherapy (20 and 100 mg) on MCS or QTcF at those study times where the bilastine plasma concentrations were highest. MCS changes for bilastine monotherapy did not exceed the normal intrasubject variance of T-wave shapes for triplicate ECG recordings. Maximum QTcF prolongation for bilastine monotherapy was 5 ms or less: 3.8 ms (90% CI 0.3, 7.3 ms) for bilastine 20 mg and 5.0 ms (90% CI 2.0, 8.0 ms) for bilastine 100 mg. There were no indications of bilastine inducing larger repolarization effects on T-wave morphology as compared with the QTcF interval, as evidenced by the similarity of z-score equivalents for placebo-corrected changes in MCS and QTcF values.

Conclusion: This study shows that bilastine, at therapeutic and supratherapeutic dosages, does not induce any effects on T-wave morphology or QTcF. These results confirm the absence of an effect for bilastine on cardiac repolarization.

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© Adis Data Information BV 2012