PURPOSE: Aclidinium bromide is a novel, long-acting, muscarinic antagonist currently in development for treatment of COPD. This Phase III study evaluated the efficacy and safety of aclidinium 200 μ g and 400 μ g BID versus placebo in the treatment of moderate to severe COPD.
METHODS: In this 12-week, double-blind, multicenter trial, patients were randomized (1:1:1) to twice-daily aclidinium 200 μ g, aclidinium 400 μ g, or placebo. Treatments were administered via the Genuair(r)* dry powder inhaler. Primary and secondary endpoints were change from baseline (mean difference between aclidinium and placebo ±SE) in trough and peak FEV1 at Week 12, respectively. Safety was assessed through adverse events (AEs), 12-lead ECGs, vital signs, and laboratory tests.
RESULTS: A total of 561 patients were randomized and 467 (83%) completed the study. Mean baseline FEV1 was similar between groups (aclidinium 200 μ g, 1358 mL; aclidinium 400 μ g, 1332 mL; placebo, 1376 mL). Mean change from baseline in trough FEV1 was significantly higher at Week 12 for 200 and 400 μ g aclidinium versus placebo (86±21 mL and 124±21 mL, respectively; p< 0.0001). Both aclidinium doses produced significantly greater mean change from baseline in trough FEV1 as compared to placebo at Weeks 1, 4, and 8 (P< 0.0001). Similarly, mean change from baseline in peak FEV1 was significantly improved for both aclidinium doses over placebo from Day 1 (P< 0.0001) through Week 12 (aclidinium 200 μ g, 146±23 mL; aclidinium 400 μ g, 192±22 mL; P< 0.0001). Rates of AEs were similar across treatment groups. Overall, the most common AE was COPD exacerbation (aclidinium 200 μ g, 9.2%; aclidinium 400 μ g, 7.4%; placebo, 12.4%). The incidence of anticholinergic AEs was low and similar across groups (dry mouth: 0.5%-1.6%; constipation: 0%-1.1%).
CONCLUSION: Aclidinium 200 μ g and 400 μ g BID provide significant bronchodilation in patients with moderate to severe COPD and both doses were well tolerated.
CLINICAL IMPLICATIONS: These results indicate that twice-daily aclidinium bromide may be a safe and effective option for the treatment of COPD. *Genuair(r) is a registered trademark of Almirall, S.A.
DISCLOSURE: Edward Kerwin, Grant monies (from sources other than industry) Dr. Kerwin has conducted clinical research trials for some 40 pharmaceutical companies including Almirall and Forest Laboratories.; Employee Dr. Garcia Gil in an employee of Almirall SA. Dr. Lakkis and Caracta are employees of Forest Research Institute.; Consultant fee, speaker bureau, advisory committee, etc. Dr. Kerwin has served on speakers panels or advisory boards for Astra Zeneca, Dey Laboratories, GlaxoSmithKline, Merck, Pfizer, Sanofi Aventis, Schering Plough, Teva Labs, and UCB Pharma. Dr. Gelb has been a speaker for Boehringer-Ingelhein, Pfizer, Astra-Zeneca and funding for clinical trials from Forest, Novartis, and GSK. Dr. D’Urzo has received research, consulting and lecturing fees from GlaxoSmithkline, Sepracor, Schering Plough, Altana, Methapharma, AstraZeneca, ONO pharma, Novartis, KOS Pharmaceuticals, Almirall SA and Forest Laboratories.; Other This study was supported by Almirall SA, Barcelona, Spain and Forest Laboratories, Inc, New York, USA.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Aclidinium bromide and the Genuair inhaler are in clinical development and has not yet been approved for its commercial use for the treatment of COPD.