PURPOSE: This study evaluated the efficacy, safety and tolerability of a novel, long-acting muscarinic antagonist, aclidinium bromide 400 μ g BID, versus placebo and tiotropium 18 μ g QD in moderate to severe COPD patients.
METHODS: In this randomized, 3-period crossover trial, patients were administered aclidinium 400 μ g BID, tiotropium 18 μ g QD, and placebo for 15 days with 9-15 days washout between treatments. The primary endpoint was change from baseline in normalized FEV1 area under the curve 0-12 hours post-dose (AUC0-12) on Day 15. Safety was assessed via adverse events (AEs), 12-lead ECGs, vitals, and laboratory tests.
RESULTS: Twenty-seven patients completed the study. At Day 15, mean change from baseline in normalized FEV1AUC0-12 was significantly greater for aclidinium (mean±standard error; 236.2±69.2 mL) and tiotropium (259.7±69.6 mL) versus placebo (15.5±69.9 mL; p< 0.001 for both). Compared to placebo, the change from baseline in morning pre-dose (trough) and peak FEV1 on Day 15 were significantly greater for aclidinium (186 #x00B1;31 mL and 277±46 mL, respectively) and tiotropium (150±31 mL and 252±47 mL, respectively; p< 0.0001 for all). On Day 1, aclidinium and tiotropium treatment produced significantly greater bronchodilation over placebo and aclidinium also resulted in significantly superior bronchodilation than tiotropium at all evening timepoints except at 23 and 24 hours post-dose. There was a significant decrease in daily rescue medication use during treatment with aclidinium and tiotropium compared to placebo (-1.5 puffs, -0.8 puffs, vs 0.5 puff, respectively, p< 0.0001). COPD symptom scores for breathlessness, cough and nighttime symptoms also improved significantly for aclidinium versus placebo. Aclidinium and tiotropium were both safe and well tolerated; diarrhea was the only AE reported by more than one patient in the aclidinium group (n=2).
CONCLUSION: In this study, aclidinium 400 μ g BID was effective and well tolerated by COPD patients. These results show that aclidinium provides significant bronchodilation and COPD symptom relief over 24 hours.
CLINICAL IMPLICATIONS: Twice-daily aclidinium treatment could be a valuable new option for the maintenance treatment of moderate to severe COPD.
DISCLOSURE: Rainard Fuhr, Employee Dr. Rainard Fuhr is an employee of PAREXEL International GmbH in Berlin, Germany, a contract research organization. Dr. Garcia Gil, Falques, and Ribera are employees of Almirall SA. Dr. Caracta is an employee of Forest Research Institute.; Consultant fee, speaker bureau, advisory committee, etc. Prof. Magnussen received fees for speaking, for organizingeducation as well as for consulting. Dr. Kirsten received fees for speaking.; 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 is in clinical development and has not yet been approved for its commercial use for the treatment of COPD.