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Objective: To assess preference, satisfaction and critical errors with a novel, breath-actuated, multi-dose dry powder inhaler (DPI; Genuair®/Pressair™), versus a widely used, single-dose DPI (HandiHaler®) in patients with moderate-to-severe chronic obstructive pulmonary disease., Methods: In this randomised, open-label, multicentre, cross-over study, patients (aged ≥ 40 years) inhaled placebo once daily through both inhalers for 2 weeks in addition to current medication. The primary end point was percentage of patients who preferred Genuair to HandiHaler. Overall patient satisfaction (5-point scale: 1 = very dissatisfied; 5 = very satisfied), critical errors and willingness to continue using each inhaler (0 = not willing; 100 = definitely willing) were assessed., Results: Of 130 patients randomised, 105 were included in the intent-to-treat population (71.4% male; mean age 65.7 years). After 2 weeks, significantly more patients preferred Genuair than HandiHaler (79.1 vs 20.9%; p < 0.0001). Overall satisfaction scores (4.6 vs 3.8; p < 0.0001) and willingness to continue use scores (84.0 vs 62.5; p < 0.0001) were significantly higher with Genuair versus HandiHaler. Significantly fewer patients made ≥ 1 critical error with Genuair only compared with HandiHaler only (2.9 vs 19.0%; p < 0.0001)., Conclusion: After 2 weeks' practice, patients preferred and were more willing to continue using Genuair than HandiHaler. Genuair was associated with higher patient satisfaction and fewer critical errors than HandiHaler.

The efficacy and safety of two doses of aclidinium bromide were evaluated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). In this 24-week, double-blind trial, patients were randomised to twice-daily aclidinium (200 μg or 400 μg) or placebo. The primary efficacy end-point was change in trough forced expiratory volume in 1 s (FEV(1)) at week 24. Other end-points included peak FEV(1), health status (St George's Respiratory Questionnaire; SGRQ) and dyspnoea (Transitional Dyspnoea Index; TDI). Overall, 828 patients were randomised. At week 24, significant improvements from baseline were observed with aclidinium 200 μg and 400 μg versus placebo for trough FEV(1) (99 and 128 mL; both p<0.0001) and peak FEV(1) (185 and 209 mL; both p<0.0001). Peak FEV(1) improvements on day 1 were comparable with week 24. Aclidinium 200 μg and 400 μg produced significant improvements over placebo in baseline-adjusted mean SGRQ total score (-3.8 and -4.6 units; p<0.001 and p<0.0001) and TDI focal score (0.6 and 1.0 units; p<0.05 and p<0.001) at week 24. With both aclidinium doses, the incidence of anticholinergic adverse events was low, and similar to placebo. Twice-daily aclidinium significantly improved bronchodilation, health status and dyspnoea, and was well tolerated in patients with COPD.

Background: This Phase III study evaluated the efficacy and safety of twice-daily aclidinium 200 μg and 400 μg versus placebo in the treatment of moderate-to-severe COPD., Methods: In this 12-week, double-blind, multicenter trial, patients were randomized (1:1:1) to inhaled twice-daily aclidinium 200 μg, aclidinium 400 μg, or placebo. Primary and secondary endpoints were changes from baseline in trough FEV₁ and peak FEV₁ at Week 12, respectively. Health status (St. George's Respiratory Questionnaire [SGRQ]), COPD symptoms (Transitional Dyspnea Index [TDI], night and early morning symptoms), and safety were also assessed., Results: A total of 561 patients (mean age, 64 ± 9 years) with a mean baseline FEV₁ of 1.36 ± 0.54 L (47.2% of predicted value) were randomized. At Week 12, aclidinium 200 μg and 400 μg showed significant improvements from baseline in mean (95% CI) trough FEV₁ compared with placebo by 86 (45, 127) mL and 124 (83,164) mL, respectively, and in peak FEV₁ by 146 (101, 190) mL and 192 (148, 236) mL, respectively (p ≤ 0.0001 for all). Both aclidinium doses also provided significant improvements in SGRQ, TDI and almost all COPD symptom scores compared with placebo (p < 0.05 for all). Incidences of adverse events (AEs) were similar across treatment groups. The incidence of anticholinergic AEs was low and similar across groups (dry mouth: 0.5%-1.6%; constipation: 0%-1.1%)., Conclusions: Treatment of moderate-to-severe COPD patients with twice-daily aclidinium 200 μg and 400 μg was associated with significant improvements in bronchodilation, health status, and COPD symptoms. Both doses were well tolerated and had safety profiles similar to placebo., Trial Registration: This ACCORD I study (AClidinium in Chronic Obstructive Respiratory Disease I) was registered on clinicaltrials.gov (NCT00891462) as "Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)".

Objective: Aclidinium bromide is a novel antimuscarinic being developed for the treatment of chronic obstructive pulmonary disease. The objective of this Phase I study was to determine the maximum tolerated dose (MTD) as well as the tolerability, safety and pharmacokinetics of aclidinium in healthy subjects., Materials and Methods: 16 healthy subjects were randomized to receive 5 single ascending doses of aclidinium 600 - 6,000 microg or placebo inhaled via dry powder inhaler, with 7 day washouts. Safety measurements included adverse events (AEs), physical examination, vital signs, pupillometry examination, clinical laboratory tests, and 12-lead electrocardiogram. Pharmacokinetic parameters of aclidinium and its metabolites were assessed., Results: The incidence of AEs was comparable between aclidinium and placebo at all doses. Most AEs were mild to moderate with no dose-related or anticholinergic/cardiac AEs. At doses >or= 2,400 microg, only 13 AEs were considered treatment related. Aclidinium (600 - 6,000 microg) did not produce function-limiting or severe AEs in >or= 50% of subjects; hence, the prospectively-defined MTD was not established. Aclidinium was rapidly converted in plasma into alcohol and carboxylic acid metabolites, and was no longer detectable after 3 hours post-dose for all doses. At lower doses, aclidinium was quantifiable only up to 1 hour post-dose in the majority of subjects. Maximum plasma concentrations for aclidinium were reached within 5 - 7 minutes (all doses) and declined rapidly. Mean elimination half-lives of aclidinium > 2,400 microg were approximately 1 hour. AUC and Cmax increased proportionately up to 4,800 microg., Conclusions: Aclidinium appears to be safe and well tolerated in single doses of 600 - 6,000 microg.