title: Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD.
abstract: OBJECTIVE
  To examine the efficacy and safety of the once-daily, inhaled, long-acting muscarinic antagonist/β2-agonist combination umeclidinium/vilanterol (UMEC/VI) compared with UMEC and VI monotherapies in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  In this 24-week, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov: NCT01313650) eligible patients were randomised 3:3:3:2 to treatment with UMEC/VI 62.5/25 mcg, UMEC 62.5 mcg, VI 25 mcg or placebo administered once daily via dry powder inhaler (N = 1532; intent-to-treat population). Primary endpoint was trough forced expiratory volume in one second (FEV1) on Day 169 (23-24 h post-dose). Additional lung-function, symptomatic, and health-related quality-of-life endpoints were assessed, including 0-6 h weighted-mean FEV1, rescue salbutamol use, Transition Dyspnoea Index (TDI), Shortness Of Breath With Daily Activity (SOBDA) and St. George's Respiratory Questionnaire (SGRQ) scores. Safety evaluations included adverse events (AEs), vital signs, 12-lead/24-h Holter electrocardiography parameters and clinical laboratory/haematology measurements.
  
  
  RESULTS
  All active treatments produced statistically significant improvements in trough FEV1 compared with placebo on Day 169 (0.072-0.167 L, all p < 0.001); increases with UMEC/VI 62.5/25 mcg were significantly greater than monotherapies (0.052-0.095 L, p ≤ 0.004). Improvements were observed for UMEC/VI 62.5/25 mcg vs placebo for weighted-mean FEV1 on Day 168 (0.242 L, p < 0.001), rescue salbutamol use during Weeks 1-24 (-0.8 puffs/day, p = 0.001), TDI (1.2 units, p < 0.001), SOBDA (-0.17 units, p < 0.001) and SGRQ (-5.51 units, p < 0.001) scores. No clinically-significant changes in vital signs, electrocardiography, or laboratory parameters were observed.
  
  
  CONCLUSIONS
  Once-daily UMEC/VI 62.5/25 mcg was well tolerated and provided clinically-significant improvements in lung function and symptoms in patients with COPD.
authors.affiliation: Department of Medicine, 111 Mason Farm Road, University of North Carolina College of Medicine, Chapel Hill, NC 27599, USA. Electronic address: james_donohue@med.unc.edu.
authors.forename: J F
authors.initials: JF
authors.lastname: Donohue
authors.forename: M R
authors.initials: MR
authors.lastname: Maleki-Yazdi
authors.forename: S
authors.initials: S
authors.lastname: Kilbride
authors.forename: R
authors.initials: R
authors.lastname: Mehta
authors.forename: C
authors.initials: C
authors.lastname: Kalberg
authors.forename: A
authors.initials: A
authors.lastname: Church
mesh_terms: D000368:Aged; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D011812:Quinuclidines; C550468:vilanterol
keywords: COPD; Fixed-dose combination; Long-acting bronchodilator; Muscarinic antagonist; Randomised; β-agonist