title: Effects of a combination of umeclidinium/vilanterol on exercise endurance in patients with chronic obstructive pulmonary disease: two randomized, double-blind clinical trials.
abstract: OBJECTIVE
  Exercise intolerance is a hallmark of chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Patients with COPD were randomized in two multicentre, double-blind, incomplete block crossover studies. Patients received two of six treatments in sequence (12 weeks each): placebo, umeclidinium (UMEC)/vilanterol (VI) (125/25 mcg or 62.5/25 mcg), VI (25 mcg) or UMEC (62.5 mcg or 125 mcg). Exercise endurance time (EET) and trough forced expiratory volume in 1 second (FEV1) (Week 12) were co-primary endpoints. Safety was monitored throughout.
  
  
  RESULTS
  Both studies showed similar 3-hour post-dose EET improvements from baseline for UMEC/VI (Week 12). Significant EET improvements were observed with both UMEC/VI doses versus placebo at Week 12 in Study 418 (UMEC/VI 125/25 mcg: 65.8 s; p = 0.005; UMEC/VI 62.5/25 mcg: 69.4 s; p = 0.003), but not in Study 417, where a placebo effect was evident. Post hoc integrated data analysis showed significant but smaller EET improvements for both UMEC/VI doses versus placebo at Week 12 (UMEC/VI 125/25 mcg: 47.5 s; p = 0.002; UMEC/VI 62.5/25 mcg: 43.7 s; p = 0.001). Both studies showed trough FEV1 improvements at Week 12 for both UMEC/VI doses. The incidence of adverse events was similar between treatment groups within each study.
  
  
  CONCLUSIONS
  UMEC/VI improved lung function and EET.
authors.affiliation: Centre de Pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, 2725 Chemin Sainte-Foy, Québec QC, G1V 4G5, Canada francois.maltais@fmed.ulaval.ca.
authors.forename: François
authors.initials: F
authors.lastname: Maltais
authors.affiliation: Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Singh
authors.affiliation: GlaxoSmithKline Research Triangle Park, North Carolina, USA.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Donald
authors.affiliation: GlaxoSmithKline, Mississauga, Ontario, Canada.
authors.forename: Glenn
authors.initials: G
authors.lastname: Crater
authors.affiliation: GlaxoSmithKline Research Triangle Park, North Carolina, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Church
authors.affiliation: GlaxoSmithKline, Shanghai, China.
authors.forename: Aik H
authors.initials: AH
authors.lastname: Goh
authors.affiliation: GlaxoSmithKline, Stockley Park West, Middlesex, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Riley
mesh_terms: D001592:Benzyl Alcohols / Q000008:administration & dosage*; D002722:Chlorobenzenes / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011812:Quinuclidines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001592:Benzyl Alcohols; D002722:Chlorobenzenes; C573971:GSK573719; D011812:Quinuclidines; C550468:vilanterol
keywords: COPD; fixed-dose combination; long-acting muscarinic antagonist; long-acting β2-adrenergic agonist