title: Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial.
abstract: BACKGROUND
  NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD). The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.
  
  
  METHODS
  Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled. Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry. The primary outcome measure was trough FEV1 at Week 12.
  
  
  RESULTS
  A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270). Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001). Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26. FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints. Transition dyspnoea index focal scores and St. George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and -2.81 (p = 0.004), respectively. NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo. NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.
  
  
  CONCLUSIONS
  Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01005901.
authors.affiliation: Department of Family and Community Medicine (DFCM), University of Toronto, Ontario, Canada. tonydurzo@sympatico.ca
authors.forename: Anthony
authors.initials: A
authors.lastname: D'Urzo
authors.forename: Gary T
authors.initials: GT
authors.lastname: Ferguson
authors.forename: Jan A
authors.initials: JA
authors.lastname: van Noord
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hirata
authors.forename: Carmen
authors.initials: C
authors.lastname: Martin
authors.forename: Rachael
authors.initials: R
authors.lastname: Horton
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Lu
authors.forename: Donald
authors.initials: D
authors.lastname: Banerji
authors.forename: Tim
authors.initials: T
authors.lastname: Overend
mesh_terms: D005260:Female; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy*; D011788:Quality of Life; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D018727:Muscarinic Antagonists; D006024:Glycopyrrolate