title: Effects of bilastine on T-wave morphology and the QTc interval: a randomized, double-blind, placebo-controlled, thorough QTc study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Informatics Group, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. cgraff@hst.aau.dk
authors.forename: Claus
authors.initials: C
authors.lastname: Graff
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Struijk
authors.forename: Jørgen K
authors.initials: JK
authors.lastname: Kanters
authors.forename: Mads P
authors.initials: MP
authors.lastname: Andersen
authors.forename: Egon
authors.initials: E
authors.lastname: Toft
authors.forename: Benoît
authors.initials: B
authors.lastname: Tyl
mesh_terms: D000328:Adult; D001372:Aza Compounds / Q000009:adverse effects*; D001562:Benzimidazoles / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones; D017408:Guidelines as Topic; D006633:Histamine Antagonists / Q000009:adverse effects*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D000077266:Moxifloxacin; D010880:Piperidines / Q000009:adverse effects*; D011804:Quinolines / Q000009:adverse effects*; D013997:Time Factors; D055815:Young Adult
chemical_list: D001372:Aza Compounds; D001562:Benzimidazoles; D024841:Fluoroquinolones; D006633:Histamine Antagonists; D010880:Piperidines; D011804:Quinolines; C445659:bilastine; D000077266:Moxifloxacin