Background and objectives: Aclidinium bromide is a long-acting muscarinic antagonist approved for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD). This 12-week phase III study evaluated efficacy and tolerability of aclidinium 200 or 400 μg in patients with moderate-to-severe COPD.
Methods: In this double-blind study, 544 patients with COPD were randomized to placebo or twice-daily aclidinium 200 or 400 μg administered by Genuair(®)/Pressair(®). Lung function, health status [measured by the St. George's Respiratory Questionnaire (SGRQ)], dyspnea [measured using the Transition Dyspnea Index (TDI)], and safety were assessed throughout the study.
Results: Mean changes from baseline in morning trough forced expiratory volume in 1 s (FEV(1)) at week 12 (primary endpoint) were significantly higher for aclidinium than for placebo (200 μg, 51 mL; 400 μg, 72 mL; both p < 0.05). Aclidinium also significantly improved other lung function outcomes. At week 12, improvements from baseline were observed with aclidinium in SGRQ total score (200 μg, -6.0; 400 μg, -5.4) and TDI focal score (200 μg, 1.0; 400 μg, 1.3). Furthermore, clinically important improvements in SGRQ total and TDI focal scores were achieved by 45 and 51 % of patients, respectively, who received aclidinium 400 μg, with a significant difference versus placebo for TDI (p < 0.05). Anticholinergic-related adverse events (e.g., dry mouth) were infrequent, occurring <2 % for any event in any treatment group. Both aclidinium doses were well tolerated.
Conclusion: This study demonstrates efficacy and safety of aclidinium in COPD patients. Unexpected baseline imbalances between treatment groups may have impacted the aclidinium treatment benefit in this study.
Trial registration: ClinicalTrials.gov NCT01045161.