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

Abstract

Walter Vincken,1 Joseph Aumann,2 Hungta Chen,3 Michelle Henley,3 Danny McBryan,4 Pankaj Goyal4 1Respiratory Division, University Hospital, UZ Brussel, Free University of Brussels, Brussels, Belgium; 2Longartsenpraktijk, Prins Bisschopssingel, Hasselt, Belgium; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 4Novartis Pharma AG, Basel, Switzerland 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. Keywords: indacaterol, glycopyrronium, inhalation therapy, bronchodilation, COPD, Breezhaler®