RESUMO
BACKGROUND: The efficacy and safety of aclidinium bromide bid, a novel, long-acting, muscarinic antagonist, was assessed in patients with moderate to severe COPD. METHODS: In this phase IIa randomized, double-blind, double-dummy, crossover trial, patients with moderate to severe COPD received aclidinium 400 µg bid, tiotropium 8 µg once daily, and placebo for 15 days, with a 9- to 15-day washout between treatment periods. Treatments were administered through the Genuair or HandiHaler dry powder inhalers. The primary end point was mean change from baseline in FEV(1) AUC(0-12/12h) (area under the curve where the numbers represent the time period for which data were collected divided by the number of hours over which the data are averaged [eg, 0-12 h postdose divided by 12 h]) on day 15. Secondary end points were changes from baseline in FEV(1) AUC(12-24/12h), FEV(1) AUC(0-24/24h), morning predose FEV(1), peak FEV(1), and COPD symptom scores. RESULTS: Thirty patients with COPD were randomized, and 27 completed the study. Mean change from baseline in FEV(1) AUC(0-12/12h) at day 15 was significantly greater for aclidinium and tiotropium over placebo (P < .0001). Mean changes from baseline in FEV(1) AUC(12-24/12h), FEV(1) AUC(0-24/24h), morning predose FEV(1), and peak FEV(1) at day 15 were significantly greater for aclidinium and tiotropium over placebo (P < .0001 for all except P < .001 for FEV(1) AUC(12-24/12h) tiotropium vs placebo). Improvements were significantly greater with aclidinium vs tiotropium on day 1 for all of the normalized AUC values of FEV(1) as well as on day 15 for FEV(1) AUC(12-24/12h) (P < .05 for all). COPD symptoms were significantly improved from baseline with aclidinium vs placebo (P < .05) but not with tiotropium. CONCLUSIONS: In patients with COPD, aclidinium 400 µg bid compared with placebo provided clinically meaningful improvements in 24-h bronchodilation that generally were comparable to tiotropium 18 µg daily but with significant differences in favor of aclidinium observed in the average nighttime period. Larger studies with longer treatment duration are ongoing to confirm the efficacy of aclidinium 400 µg bid on bronchodilation and COPD symptoms. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00868231; URL: www.clinicaltrials.gov.