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

• Published in: Journal of clinical pharmacology Vol. 52; no. 6; p. 893
• Main Authors: Tyl, Benoît, Kabbaj, Meriam, Azzam, Sara, Sologuren, Ander, Valiente, Román, Reinbolt, Elizabeth, Roupe, Kathryn, Blanco, Nathalie, Wheeler, William
• Format: Journal Article
• Language: English
• Published: England 01.06.2012
• Subjects: Adult; Anti-Allergic Agents - administration & dosage; Anti-Allergic Agents - adverse effects; Anti-Allergic Agents - blood; Anti-Allergic Agents - pharmacokinetics; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; Benzimidazoles - administration & dosage; Benzimidazoles - adverse effects; Benzimidazoles - blood; Benzimidazoles - pharmacokinetics; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Electrocardiography - drug effects; Female; Half-Life; Histamine H1 Antagonists, Non-Sedating - administration & dosage; Histamine H1 Antagonists, Non-Sedating - adverse effects; Histamine H1 Antagonists, Non-Sedating - blood; Histamine H1 Antagonists, Non-Sedating - pharmacokinetics; Humans; Ketoconazole - adverse effects; Male; Metabolic Clearance Rate - drug effects; Piperidines - administration & dosage; Piperidines - adverse effects; Piperidines - blood; Piperidines - pharmacokinetics; Young Adult
• ISSN: 1552-4604
• DOI: 10.1177/0091270011407191

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.