title: Efficacy and Safety of Umeclidinium Added to Fluticasone Propionate/Salmeterol in Patients with COPD: Results of Two Randomized, Double-Blind Studies.
abstract: Combinations of drugs with distinct and complementary mechanisms of action may offer improved efficacy in the treatment of chronic obstructive pulmonary disease (COPD). In two 12-week, double-blind, parallel-group studies, patients with COPD were randomized 1:1:1 to once-daily umeclidinium (UMEC; 62.5 μg and 125 μg) or placebo (PBO), added to twice-daily fluticasone propionate/salmeterol (FP/SAL; 250/50 μg). In both studies, the primary efficacy measure was trough forced expiratory volume in 1 second (FEV1) at Day 85. Secondary endpoints were weighted-mean (WM) FEV1 over 0-6 hours post-dose (Day 84) and rescue albuterol use. Health-related quality of life outcomes (St. George's Respiratory Questionnaire [SGRQ] and COPD assessment test [CAT]) were also examined. Safety was assessed throughout. Both UMEC+FP/SAL doses provided statistically significant improvements in trough FEV1 (Day 85: 0.127-0.148 L) versus PBO+FP/SAL. Similarly, both UMEC+FP/SAL doses provided statistically-significant improvements in 0-6 hours post-dose WM FEV1 versus PBO+FP/SAL (Day 84: 0.144-0.165 L). Rescue use over Weeks 1-12 decreased with UMEC+FP/SAL in both studies versus PBO+FP/SAL (Study 1, 0.3 puffs/day [both doses]; Study 2, 0.5 puffs/day [UMEC 125+FP/SAL]). Decreases from baseline in CAT score were generally larger for both doses of UMEC+FP/SAL versus PBO+FP/SAL (except for Day 84 Study 2). In Study 1, no differences in SGRQ score were observed between UMEC+FP/SAL and PBO+FP/SAL; however, in Study 2, statistically significant improvements were observed with UMEC 62.5+FP/SAL (Day 28) and UMEC 125+FP/SAL (Days 28 and 84) versus PBO+FP/SAL. The incidence of on-treatment adverse events across all treatment groups was 37-41% in Study 1 and 36-38% in Study 2. Overall, these data indicate that the combination of UMEC+FP/SAL can provide additional benefits over FP/SAL alone in patients with COPD.
authors.affiliation: a Midwest Chest Consultants, PC, St. Charles , Missouri , USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Siler
authors.affiliation: b Clinical Research Institute of Southern Oregon , Medford , Oregon , USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Kerwin
authors.affiliation: c GSK, Respiratory and Immuno-Inflammation, Research Triangle Park , North Carolina , USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Singletary
authors.affiliation: d GSK, Respiratory Medicines Development Centre, Stockley Park , Uxbridge , United Kingdom.
authors.forename: Jean
authors.initials: J
authors.lastname: Brooks
authors.affiliation: c GSK, Respiratory and Immuno-Inflammation, Research Triangle Park , North Carolina , USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Church
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination / Q000627:therapeutic use*; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011812:Quinuclidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D001993:Bronchodilator Agents; D000068297:Fluticasone-Salmeterol Drug Combination; C573971:GSK573719; D005938:Glucocorticoids; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D000420:Albuterol
keywords: bronchodilation; inhaled corticosteroid; long-acting beta agonist; long-acting muscarinic antagonist