title: Safety and tolerability of once-daily umeclidinium/vilanterol 125/25 mcg and umeclidinium 125 mcg in patients with chronic obstructive pulmonary disease: results from a 52-week, randomized, double-blind, placebo-controlled study.
abstract: BACKGROUND
  The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU. They are not indicated for the treatment of asthma.
  
  
  METHODS
  In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo. Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms. COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.
  
  
  RESULTS
  The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%). Headache was the most common AE in each treatment group (8-11%). AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups. No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo. The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo. With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day). Both active treatments improved lung function versus placebo.
  
  
  CONCLUSIONS
  UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD.
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. james_donohue@med.unc.edu.
authors.forename: James F
authors.initials: JF
authors.lastname: Donohue
authors.forename: Dennis
authors.initials: D
authors.lastname: Niewoehner
authors.forename: Jean
authors.initials: J
authors.lastname: Brooks
authors.forename: Dianne
authors.initials: D
authors.lastname: O'Dell
authors.forename: Alison
authors.initials: A
authors.lastname: Church
mesh_terms: D000368:Aged; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects*; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy*; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D011812:Quinuclidines; C550468:vilanterol