PURPOSE: Aclidinium bromide is a novel, long-acting muscarinic antagonist in development for the treatment of COPD. The ATTAIN study evaluated the efficacy and safety of aclidinium (200, 400 µg BID) versus placebo in patients with moderate-to-severe COPD.
METHODS: In this 24-week, double-blind, Phase III study (NCT01001494), patients were randomized (1:1:1) to aclidinium 200 µg, 400 µg, or placebo, BID. The primary endpoint was change from baseline in trough forced expiratory volume in 1 second (FEV1 ) at Weeks 12 and 24. Secondary endpoints included: trough FEV1 response over time and change from baseline in peak FEV1. Adverse events (AEs), clinical laboratory measures, vital signs, and electrocardiograms (ECGs) were assessed.
RESULTS: In total, 828 patients were randomized. Aclidinium (200, 400 µg) significantly improved trough FEV1 versus placebo: Week 12 changes from baseline in trough FEV1 were 77 mL and 105 mL for aclidinium 200, 400 µg (both p<0.0001); Week 24 increases in trough FEV1 from baseline versus placebo were 99 mL and 128 mL for aclidinium 200, 400 µg (both p<0.0001). Aclidinium (200, 400 µg) increased peak FEV1 from baseline versus placebo (185 mL and 209 mL, respectively; both p<0.0001). COPD exacerbation (200 µg, 15.9%; 400 µg, 14.1%; placebo, 20.5%) was the most frequent reason for discontinuation in all groups. Aclidinium was associated with a higher incidence of headache (10.8-12.3% vs 8.1%), nasopharyngitis (11.2-11.6% vs 8.4%), diarrhea (1.8-3.0% vs 1.1%), cough (2.5-2.6% vs 1.8%), and toothache (1.1-2.2% vs 0.4%), compared with placebo. Anticholinergic and serious AEs were low in all treatment arms; incidence of dry mouth was 0.4-0.7%. Changes in laboratory tests, vital signs, and ECGs were similar between groups.
CONCLUSIONS: Aclidinium (200, 400 µg, BID) significantly improved bronchodilation and was well tolerated in patients with moderate-to-severe COPD.
CLINICAL IMPLICATIONS: These results indicate that twice-daily aclidinium may be a valuable, effective, and safe option for the treatment of COPD. This study was supported by Almirall S.A., Barcelona, Spain, and Forest Laboratories, Inc, New York, USA.
DISCLOSURE: Paul Jones: Consultant fee, speaker bureau, advisory committee, etc.: Consultancy fees charged through my University
Eric Bateman: Grant monies (from industry related sources): Institution for clinical trial participation (not to self), Consultant fee, speaker bureau, advisory committee, etc.: Advisory Board and consultancy payments from Almirall and Forest
David Singh: Other: Received lecture fees, research grants, consultancy fees and support for conference attendance from various pharmaceutical companies including AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi and Roche
Alvar Agusti: Other: member of advisory boards, grant support and funding for accommodation and travel from Almirall
Rosa Lamarca: Employee: Almirall
Gonzalo de Miquel: Employee: Almirall
Cynthia Caracta: Employee: Forest Research Institute
Esther Garcia Gil: Employee: Almirall
Aclidinium bromide is a long-acting anti-muscarinic agent, property of Almirall S.A., which is being developed for the treatment of COPD. Aclidinium is not yet approved and the current presentation is about clinical trial results with this compound under research.