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Background: Aclidinium bromide is a novel, long-acting inhaled muscarinic antagonist currently in development for the treatment of chronic obstructive pulmonary disease (COPD). A next-generation multidose dry powder inhaler will be used for the delivery of aclidinium bromide. Objectives: To quantify whole lung deposition and regional lung deposition of aclidinium delivered by a multidose dry powder inhaler (Genuair®) in healthy subjects. Methods: A single dose (200 μg) of aclidinium bromide, radiolabelled with 99mTc, was administered from the multidose dry powder inhaler at a targeted peak inspiratory flow rate (PIFR) of 90 litres/min in 12 healthy males (18–63 years). Gamma scintigraphy was used to quantify drug deposition in the lungs and oropharynx, as well as amounts retained in the inhaler and exhaled. The quantities of drug deposited in 6 concentric regions within the lungs were also determined. Results: The mean (± SD) PIFR was 79.0 ± 9.4 litres/min. The mean (± SD) percentages of the metered dose deposited in the whole lung and oropharynx were 30.1 ± 7.3 and 54.7 ± 7.2%, respectively. Deposition of aclidinium occurred in all 6 lung zones, but was highest in the most central zone. Conclusions: These results demonstrated that the multidose dry powder inhaler delivered aclidinium efficiently to the lungs. The whole lung deposition seen in this study is an indication of the likely whole lung deposition in COPD patients who inhale with similar PIFRs; however, further studies in patients are required to confirm this.

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 (200 μg, 400 μg) or placebo, twice daily. The primary endpoint was change from baseline in trough forced expiratory volume in 1 second (FEV 1 ) at Week 24. Other study assessments at 24 weeks included: change from baseline in peak FEV 1 ; percentage of patients achieving a clinically meaningful improvement in St George9s 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 200 μg and 400 μg significantly improved trough FEV 1 from baseline compared with placebo (by 99 ml and 128 ml, respectively; both p Conclusion Aclidinium 200 μg and 400 μg 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.

SummaryBackgroundAbediterol (LAS100977) is a novel, long-acting β2-agonist, in development for the once-daily treatment of asthma in combination with mometasone. Here we report the results of a Phase IIa trial of single doses of abediterol added to ongoing maintenance therapy (inhaled corticosteroids) in patients with persistent mild-to-moderate asthma.MethodsThis was a randomised, double-blind, placebo- and active-comparator-controlled, five-way crossover study. Male patients (18–70 years) with a clinical diagnosis of persistent asthma received abediterol (5, 10 and 25 μg), salmeterol and placebo, on top of ongoing maintenance therapy. Lung function was determined using spirometry and whole body plethysmography. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) after a single dose.ResultsAll three abediterol doses induced statistically significant increases in trough FEV1 vs placebo and salmeterol. Improvements in other lung function parameters were also statistically significantly greater with all abediterol doses vs both placebo (p