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 (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.

Figure 1

GLOW6 study design. Abbreviation: od, once-daily.

Figure 2

Patient disposition, n (%).

Figure 3

Trough FEV₁ after first dose (end of day 1) and week 12 (FAS). Notes: *P<0.001. Data are least squares means ± standard error. Abbreviations: FAS, full analysis set; FEV₁, forced expiratory volume in 1 second.

Figure 4

FEV₁ from 30 minutes to 4 hours postdose and 24 hours postdose (A) on day 1 and (B) at week 12 (FAS). Notes: P<0.001 at all time points from 30 minutes to 4 hours and at 24 hours, except at 24 hours on week 12 where P<0.01. Data are least-squares means ± standard error. Abbreviations: FEV₁, forced expiratory volume in 1 second; FAS, full analysis set.

Figure 5

Subgroup analyses of treatment differences in trough FEV₁ at week 12 (FAS). Note: Data are least squares mean ± 95% CI. Abbreviations: BMI, body mass index; CI, confidence interval; FAS, full analysis set; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; LSM, least squares mean; N1, number of patients analyzed in the indacaterol + glycopyrronium treatment group; N2, number of patients analyzed in the indacaterol + placebo treatment group.

Figure 6

TDI focal score at week 12 (FAS). Note: Data are least squares means ± standard error. Abbreviations: FAS, full analysis set; TDI, transition dyspnea index.