title: Efficacy and safety of umeclidinium added to fluticasone furoate/vilanterol in chronic obstructive pulmonary disease: Results of two randomized studies.
abstract: OBJECTIVE
  The aim of these studies (NCT01957163; NCT02119286) was to evaluate the efficacy and safety of umeclidinium (UMEC 62.5 μg and 125 μg) added to fluticasone furoate/vilanterol (FF/VI, 100/25 μg) in chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  These were 12-week, double-blind, placebo-controlled, parallel-group, multicenter studies. Eligible patients were randomized 1:1:1 to treatment with once-daily blinded UMEC 62.5 μg (delivering 55 μg), UMEC 125 μg (delivering 113 μg) or placebo (PBO) added to open-label FF/VI (delivering 92/22 μg; N = 1238 [intent-to-treat population]). The primary endpoint was trough forced expiratory volume in one second (FEV1) on Day 85; the secondary endpoint was 0-6 h post-dose weighted mean (WM) FEV1 at Day 84. Health-related quality of life was reported using St George's respiratory questionnaire (SGRQ). Adverse events (AEs) were also assessed.
  
  
  RESULTS
  In both studies, trough FEV1 was significantly improved with UMEC + FF/VI (62.5 μg and 125 μg) versus PBO + FF/VI (range: 0.111-0.128 L, all p < 0.001 [Day 85]), as was 0-6 h post-dose WM FEV1 (range: 0.135-0.153 L, all p < 0.001 [Day 84]). SGRQ results were inconsistent, with statistically significant improvements with UMEC + FF/VI versus PBO + FF/VI in one study only and with UMEC 62.5 μg only (difference in SGRQ total score from baseline between treatments: -2.16, p < 0.05). Across all treatment groups, the overall incidences of AEs were similar (30-39%), as were cardiovascular AEs of special interest (<1-3%) and pneumonia AEs (0-1%).
  
  
  CONCLUSIONS
  Overall, the addition of UMEC to FF/VI therapy resulted in significant improvements in lung function compared with PBO + FF/VI in patients with COPD, with similar safety profiles, though SGRQ results were inconsistent.
  
  
  CONCLUSIONS
  The results from these two studies demonstrate that the addition of umeclidinium (62.5 μg and 125 μg) to FF/VI (100/25 μg) provides statistically significant and clinically meaningful improvements in lung function compared with placebo + FF/VI in patients with COPD. Statistically significant improvements in quality of life with UMEC + FF/VI versus placebo + FF/VI were reported in one study only. Safety profiles were consistent across all treatment groups in both studies. These studies support the use of triple therapy in COPD, providing physicians with an alternative treatment option.
authors.affiliation: Midwest Chest Consultants, PC, 330 First Capitol Drive, Suite 470, St Charles, MO, USA. Electronic address: thomas.siler.md@midwestchest.com.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Siler
authors.affiliation: Clinical Research Institute of Southern Oregon, Medford, OR, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Kerwin
authors.affiliation: GSK, Respiratory Medicines Development Centre, Stockley Park, Middlesex, UK.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Sousa
authors.affiliation: GSK, Respiratory and Immuno-Inflammation, Research Triangle Park, NC, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Donald
authors.affiliation: GSK, Respiratory Medicines Development Centre, Stockley Park, Middlesex, UK.
authors.forename: Rehan
authors.initials: R
authors.lastname: Ali
authors.affiliation: GSK, Respiratory and Immuno-Inflammation, Research Triangle Park, NC, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Church
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use; D000368:Aged; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D001592:Benzyl Alcohols / Q000009:adverse effects / Q000627:therapeutic use*; D002722:Chlorobenzenes / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; 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*; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D005938:Glucocorticoids; D018727:Muscarinic Antagonists; D011812:Quinuclidines; C550468:vilanterol; C523187:fluticasone furoate
keywords: Bronchodilation; Inhaled corticosteroid; Long-acting beta(2) agonist; Long-acting muscarinic antagonist