PURPOSE: ATTAIN investigated the efficacy and safety of twice-daily aclidinium bromide (200 and 400 µg), a long-acting muscarinic antagonist, on symptoms and health status in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
METHODS: In this 24-week, double-blind, Phase III study (NCT01001494), patients were randomized (1:1:1) to aclidinium 200, 400 µg or placebo, twice-daily. Dyspnea was assessed using the Transitional Dyspnea Index (TDI), and symptoms by daily electronic diaries using the EXACT Respiratory Symptoms (E-RS) scores, and a night-time and early-morning symptoms questionnaire. Health status was assessed using the St George’s Respiratory Questionnaire (SGRQ).
RESULTS: In total 828 patients were randomized. At Week 24, more patients treated with aclidinium (200, 400 µg) reached a clinically relevant improvement in TDI focal score (≥1 unit) vs placebo (53.3% and 56.9% vs 45.5%; p=0.032 and 0.004, respectively). Aclidinium significantly reduced E-RS scores vs placebo: RS-breathlessness (range 0-17) (200 µg, -0.8 [p≤0.0001]; 400 µg, -1.05 [p≤0.0001]); RS-chest (range 0-12) (200 µg, -0.33 [p≤0.003]; 400 µg, -0.52 [p≤0.0001]); and RS-cough and sputum (range 0-11) (200 µg, -0.21 [p≤0.03]; 400 µg, -0.44 [p≤0.0001]) at Week 24. Aclidinium reduced the incidence of night-time (p<0.001) and early-morning (p<0.01) symptoms and was associated with more days without reliever medication (p=0.0003), vs placebo. At Week 24, more patients had a clinically relevant improvement in SGRQ total score with aclidinium 200 and 400 µg vs placebo (54.9% and 54.3% vs 39.5%; p=0.0004 and 0.0014, respectively); the improvement with aclidinium 400 µg vs placebo was 4.3 units, p<0.0001. SGRQ domain scores (Symptoms, Activity, Impacts) were also significantly improved with aclidinium (200, 400 µg) vs placebo at Week 24 (p<0.05 all domains).
CONCLUSIONS: Aclidinium 200 and 400 µg BID provided statistically significant and clinically relevant improvements in COPD symptoms and health status in patients with COPD.
CLINICAL IMPLICATIONS: These results indicate that aclidinium could be a valuable new treatment option for 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
Alvar Agusti: Other: Member of advisory boards, grant support and funding for accommodation and travel from Almirall
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: Lecture fees, research grants, consultancy fees and support for conference attendance from various pharmaceutical companies including AstraZeneca, GlaxoSmithKline, Chiesi, Boehringer Ingelheim and Roche
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 presetnation is about clinical trial results with this compound under research.