title: No cardiac effects of therapeutic and supratherapeutic doses of rupatadine: results from a 'thorough QT/QTc study' performed according to ICH guidelines.
abstract: OBJECTIVE
  To evaluate the effects of therapeutic and supratherapeutic doses of rupatadine on cardiac repolarization in line with a 'thorough QT/QTc study' protocol performed according to International Conference on Harmonization guidelines.
  
  
  METHODS
  This was a randomized (gender-balanced), parallel-group study involving 160 healthy volunteers. Rupatadine, 10 and 100 mg day(-1), and placebo were administered single-blind for 5 days, whilst moxifloxacin 400 mg day(-1) was given on days 1 and 5 in open-label fashion. ECGs were recorded over a 23-h period by continuous Holter monitoring at baseline and on treatment days 1 and 5. Three 10-s ECG samples were downloaded at regular intervals and were analysed independently. The primary analysis of QTc was based on individually corrected QT (QTcI). Treatment effects on QTcI were assessed using the largest time-matched mean difference between the drug and placebo (baseline-subtracted) for the QTcI interval. A negative 'thorough QT/QTc study' is one where the main variable is around < or =5 ms, with a one-sided 95% confidence interval that excludes an effect >10 ms.
  
  
  RESULTS
  The validity of the trial was confirmed by the fact that the moxifloxacin-positive control group produced the expected change in QTcI duration (around 5 ms). The ECG data for rupatadine at both 10 and 100 mg showed no signal effects on the ECG, after neither single nor repeated administration. Furthermore, no pharmacokinetic/pharmacodynamic relationship, gender effects or clinically relevant changes in ECG waveform outliers were observed. No deaths or serious or unexpected adverse events were reported.
  
  
  CONCLUSIONS
  This 'thorough QT/QTc study' confirmed previous experience with rupatadine and demonstrated that it had no proarrhythmic potential and raised no concerns regarding its cardiac safety.
authors.affiliation: Clinical Development Unit, J Uriach y Compañía, Palau-solità i Plegamans, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Donado
authors.forename: Iñaki
authors.initials: I
authors.lastname: Izquierdo
authors.forename: Iñaki
authors.initials: I
authors.lastname: Pérez
authors.forename: Olga
authors.initials: O
authors.lastname: García
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Antonijoan
authors.forename: Ignaci
authors.initials: I
authors.lastname: Gich
authors.forename: Anna
authors.initials: A
authors.lastname: Solans
authors.forename: Juana
authors.initials: J
authors.lastname: Peña
authors.forename: Joel
authors.initials: J
authors.lastname: Morganroth
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Barbanoj
mesh_terms: D000293:Adolescent; D000328:Adult; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D013997:Time Factors; D055815:Young Adult
chemical_list: D018926:Anti-Allergic Agents; D039563:Histamine H1 Antagonists, Non-Sedating; D010972:Platelet Activating Factor; C103639:rupatadine; D003533:Cyproheptadine
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