Dose response of umeclidinium administered once or twice daily in patients with COPD: a pooled analysis of two randomized, double-blind, placebo-controlled studies.
Umeclidinium (UMEC) is an inhaled long-acting muscarinic antagonist approved in the US and EU for the once-daily (QD) treatment of chronic obstructive pulmonary disease (COPD); it is not indicated for the treatment of asthma. To fully characterize the dose-response relationship of UMEC in patients with COPD, a pooled analysis of data from two randomized, placebo-controlled, cross-over, dose-ranging studies was performed, evaluating UMEC at doses of 15.6-1000 mcg QD and 15.6-250 mcg twice daily (BID). The primary endpoint was trough forced expiratory volume in one second (FEV(1)) at the end of each study's treatment period (Day 8/Day 15). A population model-based analysis using total daily UMEC dose was used for the primary analysis comparing QD and BID dosing. A physiological effect (E(max)) model was optimal in defining the relationship between UMEC dose and the primary endpoint, demonstrating a clear monotonic dose response over QD and BID dosing regimens. UMEC doses ≥62.5 mcg QD were differentiated from lower doses and BID dosing did not provide benefit over QD dosing. The potency (ED(50)) estimate was 33 mcg with QD dosing. These data indicate that UMEC 62.5 mcg and 125 mcg QD provide lung function benefits that warrant further investigation for the treatment of COPD.
['Donohue|James F|JF|', 'Kalberg|Christopher|C|', 'Shah|Palvi|P|', 'Beerahee|Misba|M|', 'Mehta|Rashmi|R|', 'Gunawan|Rudy|R|', 'Church|Alison|A|']
D000368:Aged D001993:Bronchodilator Agents D018592:Cross-Over Studies D004305:Dose-Response Relationship, Drug D004311:Double-Blind Method D004334:Drug Administration Schedule D005260:Female D005541:Forced Expiratory Volume D006801:Humans D008297:Male D008875:Middle Aged D018727:Muscarinic Antagonists D029424:Pulmonary Disease, Chronic Obstructive D011812:Quinuclidines D012602:Scopolamine Derivatives D000069447:Tiotropium Bromide
umeclidinium COPD long-acting muscarinic antagonist LAMA