Alvar Agusti

P255 ATTAIN: twice-daily aclidinium bromide in patients with moderate to severe chronic obstructive pulmonary disease

Introduction and Objectives The Phase III ATTAIN study investigated the effect of two twice daily doses of aclidinium bromide, a second-generation, long-acting muscarinic antagonist with low systemic activity, in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods In this 24-week, double-blind study, patients were randomised (1:1:1) to receive aclidinium (200u2005μg, 400u2005μg) or placebo, twice daily. The primary endpoint was change from baseline in trough forced expiratory volume in 1 second (FEV1) at Week 24. Other study assessments at 24u2005weeks included: change from baseline in peak FEV1; percentage of patients achieving a clinically meaningful improvement in St Georges Respiratory Questionnaire total score and Transition Dyspnoea Index; COPD symptoms as assessed by the EXACT Respiratory Symptoms score; exacerbation rate based on two definitions (healthcare resource utilisation and EXAcerbations of Chronic pulmonary disease Tool). Adverse events (AEs), clinical laboratory measures, vital signs and ECGs were also assessed. Results A total of 819 patients were included in intention-to-treat (ITT) and safety populations. At Week 24, aclidinium 200u2005μg and 400u2005μg significantly improved trough FEV1 from baseline compared with placebo (by 99u2005ml and 128u2005ml, respectively; both p<0.0001). Aclidinium was significantly superior to placebo at Week 24 for all other study assessments (Abstract P255 table 1). Aclidinium was well tolerated and the incidence of anticholinergic AEs was low and similar to placebo. Changes in laboratory tests, vital signs and ECGs were similar between all groups.Abstract P255 Table 1 Study assessments at Week 24 (ITT population) Placebo twice daily n=273 Aclidinium 200u2005μg twice daily n=277 Aclidinium 400u2005μg twice daily n=269 Change from baseline in trough FEV1 vs placebo (ml) (±SE) – 99*** (0.02) 128*** (0.02) Change from baseline in peak FEV1 vs placebo (ml) (±SE) – 185*** (0.02) 209*** (0.02) Clinically meaningful improvement (≥1 unit) in TDI focal score (% patients) 45.5 53.3* 56.9** Clinically meaningful improvement (≥4 units) in SGRQ total score (% patients) 39.5 54.9*** 54.3*** E-RS total score (±SE) −0.43 (0.53) −3.59*** (0.52) −4.08*** (0.53) Exacerbation frequency, HCRU (rate ratio vs placebo) (95% CI) – 0.72* (0.52 to 0.99) 0.67* (0.48 to 0.94) Exacerbation frequency, EXACT (rate ratio vs placebo) (95% CI) – 0.72* (0.55 to 0.94) 0.71* (0.54 to 0.93) *p<0.05, **p<0.01, ***p<0.001 vs placebo. ER-S, EXACT Respiratory Symptoms; EXACT, EXAcerbations of Chronic pulmonary disease Tool; FEV1, forced expiratory volume in 1 second; HCRU, healthcare resource utilisation; SGRQ, St Georges Respiratory Questionnaire; TDI, Transition Dyspnoea Index. Conclusion Aclidinium 200u2005μg and 400u2005μg twice daily provided clinically meaningful improvements in bronchodilation, health status, symptoms, breathlessness and exacerbation rate. Aclidinium was well tolerated with a similar safety profile for both doses; the incidence of AEs was similar to placebo.