Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

BACKGROUND: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). METHODS: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1<80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation. RESULTS: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p<0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p<0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies. CONCLUSION: Aclidinium is effective and well tolerated in patients with moderate to severe COPD

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

SummaryBackgroundAclidinium bromide is a novel, long-acting, inhaled muscarinic 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.MethodsThis double-blind, randomised, placebo-controlled, crossover study was conducted in patients with moderate to severe COPD (forced expiratory volume in 1s [FEV1] <65% predicted). Patients were randomly assigned to one of four treatment sequences of aclidinium bromide 100, 300, 900μg and placebo with a washout period between doses. The primary outcome was area under the FEV1 curve over the 0–24h time interval.ResultsSeventeen patients with COPD were studied. Mean FEV1 over 24h was 1.583L for placebo, and 1.727L, 1.793L and 1.815L for aclidinium bromide 100, 300 and 900μg, respectively (p<0.001 vs. placebo, all doses). Significant changes from baseline in FEV1 were detected 15min post-dose for aclidinium bromide 300 and 900μg, with a peak effect 2h 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.ConclusionAclidinium bromide 100–900μg produced sustained bronchodilation over 24h in patients with COPD