title: Efficacy and safety of coadministration of once-daily indacaterol and glycopyrronium versus indacaterol alone in COPD patients: the GLOW6 study.
abstract: BACKGROUND
  Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.
  
  
  METHODS
  In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices). The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.
  
  
  RESULTS
  A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001). IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01). TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05). The incidence of adverse events was similar for the two treatment groups.
  
  
  CONCLUSIONS
  In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.
authors.affiliation: Respiratory Division, University Hospital, UZ Brussel, Free University of Brussels, Brussels, Belgium.
authors.forename: Walter
authors.initials: W
authors.lastname: Vincken
authors.affiliation: Longartsenpraktijk, Prins Bisschopssingel, Hasselt, Belgium.
authors.forename: Joseph
authors.initials: J
authors.lastname: Aumann
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Hungta
authors.initials: H
authors.lastname: Chen
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Henley
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Danny
authors.initials: D
authors.lastname: McBryan
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Goyal
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005541:Forced Expiratory Volume; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D007320:Inspiratory Capacity; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D007189:Indans; D018727:Muscarinic Antagonists; D015363:Quinolones; C510790:indacaterol; D006024:Glycopyrrolate
keywords: Breezhaler®; COPD; bronchodilation; glycopyrronium; indacaterol; inhalation therapy