Aclidinium bromide, a long-acting antimuscarinic, does not affect QT interval in healthy subjects

J Clin Pharmacol. 2011 Jun;51(6):923-32. doi: 10.1177/0091270010374471. Epub 2010 Oct 19.

Abstract

In this phase I trial, the effect of aclidinium, a novel, inhaled long-acting muscarinic antagonist, on QT interval was evaluated, and its cardiovascular safety was assessed in 272 healthy subjects. Aclidinium 200 µg, aclidinium 800 µg, matching placebo, or open-label moxifloxacin 400 mg was administered daily for 3 days. The primary outcome was mean change in individual heart rate-corrected QT interval (QTcI). Secondary measures included Bazett-corrected QT interval (QTcB), Fridericia-corrected (QTcF) intervals, 12-lead electrocardiogram (ECG) readings, and 24-hour 12-lead Holter ECG parameters. Adverse events, vital signs, and laboratory and pharmacokinetic parameters were also assessed. Maximum mean QTcI change from time-matched baseline on day 3 was -1.0 milliseconds at 2 hours for aclidinium 200 µg, -1.8 milliseconds at 5 minutes for 800 µg, +11.0 milliseconds at 4 hours for moxifloxacin, and -1.2 milliseconds at 23.5 hours for placebo. Aclidinium had no significant effects on secondary ECG measures. Aclidinium plasma concentrations were generally below the lower limit of quantitation (0.05 ng/mL) after 200 µg and were detected only up to 1 hour after the 800-µg dose in the majority of cases. It is concluded that aclidinium bromide, at doses up to 800 µg, has a favorable cardiovascular safety profile with no effect on QT interval.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Anti-Infective Agents / adverse effects
  • Aza Compounds / adverse effects
  • Electrocardiography / drug effects*
  • Electrocardiography / methods*
  • Electrocardiography, Ambulatory / drug effects*
  • Electrocardiography, Ambulatory / methods
  • Female
  • Fluoroquinolones
  • Humans
  • Male
  • Middle Aged
  • Moxifloxacin
  • Muscarinic Antagonists / adverse effects*
  • Muscarinic Antagonists / pharmacokinetics
  • Quinolines / adverse effects
  • Tropanes / adverse effects*
  • Tropanes / pharmacokinetics

Substances

  • Anti-Infective Agents
  • Aza Compounds
  • Fluoroquinolones
  • Muscarinic Antagonists
  • Quinolines
  • Tropanes
  • Moxifloxacin
  • aclidinium bromide