Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study

Edward Kerwin, Jacques Hébert, Nicola Gallagher, Carmen Martin, Tim Overend, Vijay K T Alagappan, Yimeng Lu, Donald Banerji, Edward Kerwin, Jacques Hébert, Nicola Gallagher, Carmen Martin, Tim Overend, Vijay K T Alagappan, Yimeng Lu, Donald Banerji

Abstract

NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD). The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks. Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks. Primary end-point was trough forced expiratory volume in 1 s (FEV(1)) at 12 weeks. 1,066 patients were randomised, 810 completed the study. At week 12, trough FEV(1) increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001). Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001). NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo. NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes. Safety profiles were similar across groups. NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium. NVA237 can potentially be an alternative choice of LAMA for COPD patients.

Trial registration: ClinicalTrials.gov NCT00929110.

Conflict of interest statement

Statement of Interest

A statement of interest for all authors, and for the study itself, can be found at www.erj.ersjournals.com/site/misc/statements.xhtml

Figures

Figure 1–
Figure 1–
GLOW2 study design.
Figure 2–
Figure 2–
Patient disposition.
Figure 3–
Figure 3–
Trough forced expiratory volume in 1 s (FEV1) at day 1 and weeks 12, 26 and 52. Data presented as least squares mean±se. ***: p<0.001 versus placebo; #: p=0.007 versus tiotropium.
Figure 4–
Figure 4–
Serial spirometry on a) day 1, b) week 12 and c) week 52. a) NVA237 superior to placebo at all assessed time points (pversus placebo all time points statistically significant (p<0.05) except 16 h, 23 h 15 min and 23 h 45 min. c) NVA237 superior to placebo at all assessed time points (p<0.01), superior to tiotropium at 5 min,15 min and 30 min, and 1, 2 and 3 h (p<0.05). FEV1: forced expiratory volume in 1 s.
Figure 5–
Figure 5–
Kaplan–Meier plot of the time to first moderate or severe chronic obstructive pulmonary disease exacerbation.

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Source: PubMed

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