Bronchodilatory effects of aclidinium bromide, a long-acting muscarinic antagonist, in COPD patients

Background: Aclidinium bromide is a novel, long-acting, inhaled muscannic antagonist bronchodilator currently in Phase III clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the pharmacodynamics, pharmacokinetics, safety and tolerability of ascending doses of aclidinium bromide in patients with COPD. Methods: This double-blind, randomised, placebo-controlled, crossover study was conducted in patients with moderate to severe COPD (forced expiratory volume in 1 s [FEV1] < 65% predicted). Patients were randomly assigned to one of four treatment sequences of aclidinium bromide 100, 300, 900 jig and placebo with a washout period between doses. The primary outcome was area under the FEV1 curve over the 0-24 h time interval. Results: Seventeen patients with COPD were studied. Mean FEV1 over 24 h was 1.583 L for placebo, and 1.727 L, 1.793 L and 1.815 L for aclidinium bromide 100, 300 and 900 mu g, respectively (p < 0.001 vs placebo, all doses). Significant changes from baseline in FEV1 were detected 15 min post-dose for aclidinium bromide 300 and 900 mu g, with a peak effect 2 h post-dose (all doses). Aclidinium bromide was undetected in plasma. The majority of adverse events was unrelated to study medication and did not result in discontinuation. Conclusion: Aclidinium bromide 100-900 mu g produced sustained bronchodilation over 24 h in patients with COPD. (C) 2009 Elsevier Ltd. All rights reserved.