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

J Clin Pharmacol. 2012 Jun;52(6):893-903. doi: 10.1177/0091270011407191. Epub 2011 Jun 3.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • Adult
  • Anti-Allergic Agents / administration & dosage
  • Anti-Allergic Agents / adverse effects*
  • Anti-Allergic Agents / blood
  • Anti-Allergic Agents / pharmacokinetics
  • 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

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-Allergic Agents
  • Benzimidazoles
  • Histamine H1 Antagonists, Non-Sedating
  • Piperidines
  • bilastine
  • Ketoconazole