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Aclidinium Bromide, a Long‐Acting Antimuscarinic, Does Not Affect QT Interval in Healthy Subjects
Author(s) -
Lasseter Kenneth C.,
Aubets Jordi,
Chuecos Ferran,
Gil Esther Garcia
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010374471
Subject(s) - qt interval , moxifloxacin , medicine , placebo , anesthesia , confidence interval , cardiology , chemistry , biochemistry , alternative medicine , pathology , antibiotics
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 Bazettcorrected 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.