Aclidinium bromide, a long-acting antimuscarinic, does not affect QT interval in healthy subjects.
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.
Clinical Pharmacology of Miami, 550 West 84th Street, Miami, FL 33014, USA. klasseter@clinpharmmiami.com
Kenneth C
KC
Lasseter
Jordi
J
Aubets
Ferran
F
Chuecos
Esther Garcia
EG
Gil
D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects; D001372:Aza Compounds / Q000009:adverse effects; D004562:Electrocardiography / Q000187:drug effects* / Q000379:methods*; D015716:Electrocardiography, Ambulatory / Q000187:drug effects* / Q000379:methods; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D018727:Muscarinic Antagonists / Q000009:adverse effects* / Q000493:pharmacokinetics; D011804:Quinolines / Q000009:adverse effects; D014326:Tropanes / Q000009:adverse effects* / Q000493:pharmacokinetics
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D018727:Muscarinic Antagonists; D011804:Quinolines; D014326:Tropanes; D000077266:Moxifloxacin; C542859:aclidinium bromide