Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

Paul W Jones, Stephen I Rennard, Alvar Agusti, Pascal Chanez, Helgo Magnussen, Leonardo Fabbri, James F Donohue, Eric D Bateman, Nicholas J Gross, Rosa Lamarca, Cynthia Caracta, Esther Garcia Gil, Paul W Jones, Stephen I Rennard, Alvar Agusti, Pascal Chanez, Helgo Magnussen, Leonardo Fabbri, James F Donohue, Eric D Bateman, Nicholas J Gross, Rosa Lamarca, Cynthia Caracta, Esther Garcia Gil

Abstract

Background: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Methods: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1<80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.

Results: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p<0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p<0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies.

Conclusion: Aclidinium is effective and well tolerated in patients with moderate to severe COPD.

Trial registration: ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II).

Figures

Figure 1
Figure 1
Patient disposition in a) ACCLAIM/COPD I, and b) ACCLAIM/COPD II
Figure 2
Figure 2
Trough forced expiratory volume in 1 second for aclidinium 200 μg versus placebo over 52 weeks in ACCLAIM/COPD I and II
Figure 3
Figure 3
Percentage of patients with a clinically relevant improvement in St George's Respiratory Questionnaire total score (≥4 units) over time in ACCLAIM/COPD I and II
Figure 4
Figure 4
Kaplan-Meier survival curves for the time to first moderate or severe chronic obstructive pulmonary disease exacerbation in ACCLAIM/COPD I and II

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