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.

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 (AUC_30min–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 AUC_30min–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®

Supplementary materials

Table S1 List of study centers

Table S2 Medications allowed in the GLOW6 study under certain conditions

Table S3 Procedure for handling missing data in the GLOW6 study

Acknowledgments

The study was sponsored by Novartis Pharma AG. The authors were assisted in the preparation of the manuscript by Shilpa Mudgal, a professional medical writer contracted to CircleScience (Macclesfield, UK), and Mark J Fedele (Novartis). The authors would also like to thank Damon Jack (Novartis) for his contribution to the study conduct and manuscript preparation. Writing support was funded by the study sponsor. ClinicalTrials.gov identifier: NCT1604278.

Disclosure

WV has acted as consultant for Boehringer Ingelheim/Pfizer, GlaxoSmithKline, AstraZeneca, Meda Pharmaceuticals, Chiesi, Mundipharma, Novartis, and MSD. JA has no conflicts of interest. HC, MH, DMcB, and PG are employees of the study sponsor and have no other conflicts to declare.