Introduction and Objective Aclidinium bromide is a novel, long-acting, muscarinic antagonist indicated as a maintenance treatment for chronic obstructive pulmonary disease (COPD). Maintaining significant bronchodilation throughout the 24-hour day is important to improve outcomes for patients with COPD. This study evaluated daily bronchodilatory symptom control with twice-daily (BID) aclidinium in patients with stable, moderate-to-severe COPD.
Methods In this 6-week, randomised, double-blind, Phase IIIb study, patients received aclidinium 400 µg (metered dose; equivalent to aclidinium 322 µg delivered dose) BID, tiotropium bromide 18 µg once daily or placebo. Change from baseline in normalised forced expiratory volume in 1 second (FEV1) area under the curve over the 24-hour period immediately following morning treatment (AUC0–24) at Week 6 was the primary endpoint. Other endpoints included change from baseline in normalised FEV1 AUC12–24 and AUC0–12, pre-dose (trough) FEV1 and peak FEV1. Daily symptoms were recorded each evening using the 11-item EXAcerbations of Chronic pulmonary disease Tool-Respiratory Symptoms (EXACT-RS) and a total score was calculated (range 040: more severe symptoms indicated by higher score). Additional daily symptoms, including presence of morning symptoms and night-time symptom severity (5point scale: 0=none; 4=very severe), were recorded using electronic diaries.
Results In total, 414 patients were randomised: mean age was 62.3±8.1 years (mean±SD); 54.1% were current smokers; baseline FEV1 was 1.484±0.51 L At Week 6, aclidinium 400 µg BID and tiotropium 18 µg QD significantly improved lung function from baseline compared with placebo (Table). Compared with placebo, aclidinium and tiotropium significantly reduced EXACT-RS total scores from baseline (–2.1 and –1.3 versus –0.1; p<0.0001 and p<0.05, respectively), and increased percentage of days without morning symptoms from baseline (6.7% and 3.4%, respectively, versus 2.2%; p<0.05 for both) at Week 6. Night-time symptom severity scores were significantly reduced from baseline with aclidinium (–0.16) versus placebo (–0.02) at Week 6 (p<0.05) but improvements with tiotropium (–0.09) did not reach statistical significance.
Conclusions Aclidinium 400 µg BID provided significant 24-hour bronchodilation and daily symptom improvement throughout the study. The bronchodilatory effect of aclidinium was similar to tiotropium, with numerically greater improvement in morning and night-time symptoms among aclidinium-treated patients.