An integrated review to evaluate dose response of umeclidinium (GSK573719) administered once or twice daily in Subjects with COPD

Trial description: The purpose of this study was to assess the total daily dose response of umeclidinium using pooled data from study AC4113073 and AC4115321 (excluding the site with Investigator ID of 040688) following once daily doses of umeclidinium (15.6, 31.25, 62.5, 125, 250, 500, and 1000mcg) and twice daily doses of umeclidinium (15.6, 31.25 62.5, 125, and 250mcg) compared with placebo in subjects with chronic obstructive pulmonary disease (COPD). Study AC4113073 was a multicentre, randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over, incomplete block design study to evaluate the safety and efficacy of five doses of the long-acting muscarinic receptor antagonist umeclidinium (GSK573719) (62.5mcg, 125mcg, 250mcg, 500mcg, and 1000mcg) administered once-daily and three doses of umeclidinium (62.5mcg, 125mcg, and 250mcg) administered twice-daily compared with placebo over a 14 day treatment period in subjects with chronic obstructive pulmonary disease (COPD). Study AC4115321 was a multicenter, randomized, double-blind, placebo controlled, three way crossover, incomplete block study to evaluate the dose response of 4 doses of umeclidinium Inhalation Powder (15.6 mcg, 31.25 mcg, 62.5 mcg, and 125mcg) administered once daily over a 7 day treatment period in patients with COPD. Study AC4115321 also evaluated the safety and efficacy of the 4 doses of umeclidinium (15.6 mcg, 31.25 mcg, 62.5 mcg, and 125 mcg) administered once daily and 2 doses of umeclidinium (15.6 mcg and 31.25 mcg) administered twice daily compared with placebo over 7 days in subjects with COPD. An open label tiotropium (18mcg once-daily) group was included as an active control in both studies. This meta-analysis combined the two studies’ data together to evaluate the dose response of umeclidinium to better inform dose selection of umeclidinium.