title: Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis.
abstract: 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.
authors.affiliation: Robert Ballanger’s Hospital, Department of Cardiology, Aulnay Sous Bois, France. tyl@noos.fr
authors.forename: Benoît
authors.initials: B
authors.lastname: Tyl
authors.forename: Meriam
authors.initials: M
authors.lastname: Kabbaj
authors.forename: Sara
authors.initials: S
authors.lastname: Azzam
authors.forename: Ander
authors.initials: A
authors.lastname: Sologuren
authors.forename: Román
authors.initials: R
authors.lastname: Valiente
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Reinbolt
authors.forename: Kathryn
authors.initials: K
authors.lastname: Roupe
authors.forename: Nathalie
authors.initials: N
authors.lastname: Blanco
authors.forename: William
authors.initials: W
authors.lastname: Wheeler
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000328:Adult; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006207:Half-Life; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007654:Ketoconazole / Q000009:adverse effects*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018926:Anti-Allergic Agents; D001562:Benzimidazoles; D039563:Histamine H1 Antagonists, Non-Sedating; D010880:Piperidines; C445659:bilastine; D007654:Ketoconazole