Introduction and objective Maintaining bronchodilation and symptom control throughout the day and night is an important COPD therapeutic aim. Here, we compare 24-hour lung function and symptom control in symptomatic patients with moderate to severe COPD treated with aclidinium or tiotropium, two long-acting, muscarinic antagonists.
Methods This was a post-hoc analysis of a 6-week, double-blind, Phase IIIb study comparing aclidinium 400 µg BID with tiotropium bromide 18 µg QD or placebo in patients with moderate to severe COPD (NCT01462929). Symptomatic patients were defined as having an EXAcerbations of Chronic pulmonary disease Tool-Respiratory Symptoms (E-RS) baseline score ≥ 10 units. Primary endpoint: change from baseline in normalised FEV1 AUC over 24-hours post-morning dose (AUC–24/24h) at Week 6. Other endpoints: change from baseline in morning pre-dose (trough) FEV1 and change from baseline in FEV1 AUC0-–2/12h; 12-–4/12h, E-RS, early-morning and night-time symptoms, and limitation of early-morning activities.
Results A total of 277/414 symptomatic patients were included; mean age was 62.1 years, 54.5% were current smokers, baseline FEV1 1.41 ± 0.48 L. At Week 6, aclidinium 400 µg BID improved FEV1 over 24 h from baseline vs placebo (Table 1). During the night-time period, aclidinium 400 µg BID improved FEV1 from baseline vs tiotropium 18 µg QD. At Week 6, improvements in trough FEV1 from baseline were observed with aclidinium vs tiotropium and placebo. Aclidinium improved E-RS total score from baseline vs tiotropium and placebo. Moreover, aclidinium improved early-morning and night-time symptom severity from baseline vs tiotropium and placebo over the treatment period (see Table 1 for all results described above). Limitation of early-morning activities caused by COPD symptoms was also improved with aclidinium vs tiotropium and placebo (p < 0.05). Tolerability has been previously reported (Beier COPD 2013) where adverse events (AEs) were similar in each arm, few anticholinergic AEs or serious AEs occurred in any group, and aclidinium was well tolerated.
Conclusions Aclidinium 400 µg BID improved bronchodilation, particularly during the night-time period, as well as early morning, daily and night-time symptoms, and early-morning limitation of activity in symptomatic patients compared with either tiotropium 18 µg QD or placebo.