Efficacy and safety of coadministration of once-daily indacaterol and glycopyrronium versus indacaterol alone in COPD patients: the GLOW6 study

Int J Chron Obstruct Pulmon Dis. 2014 Feb 24;9:215-28. doi: 10.2147/COPD.S51592. eCollection 2014.

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.

Materials and 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01604278.

Keywords: Breezhaler®; COPD; bronchodilation; glycopyrronium; indacaterol; inhalation therapy.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Aged
  • Area Under Curve
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Europe
  • Female
  • Forced Expiratory Volume
  • Glycopyrrolate / administration & dosage*
  • Glycopyrrolate / adverse effects
  • Humans
  • Indans / administration & dosage*
  • Indans / adverse effects
  • Inspiratory Capacity
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage*
  • Muscarinic Antagonists / adverse effects
  • Nebulizers and Vaporizers
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quinolones / administration & dosage*
  • Quinolones / adverse effects
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Vital Capacity

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Indans
  • Muscarinic Antagonists
  • Quinolones
  • indacaterol
  • Glycopyrrolate

Associated data

  • ClinicalTrials.gov/NCT01604278