Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial

• Published in: International journal of chronic obstructive pulmonary disease Vol. 7; no. default; pp. 503 - 513
• Main Authors: Beeh, Kai M, Singh, Dave, Di Scala, Lilla, Drollmann, Anton
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2012; Dove Medical Press
• Subjects: Adult; Aged; Aged, 80 and over; Care and treatment; Complications and side effects; Cross-Over Studies; Dosage and administration; Drug Administration Schedule; Drug therapy; Exercise; Exercise Test; Exercise Tolerance - drug effects; Female; Forced Expiratory Volume; Functional Residual Capacity; Glycopyrrolate; Glycopyrrolate - administration & dosage; Glycopyrrolate - adverse effects; Humans; Lung - drug effects; Lung - physiopathology; Lung diseases, Obstructive; Lung Volume Measurements; Male; Middle Aged; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - adverse effects; Original Research; Physiological aspects; Plethysmography; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Recovery of Function; Residual Volume; Severity of Illness Index; Spirometry; Time Factors; Treatment Outcome; United Kingdom; Switzerland; NVA237; exercise tolerance; FEV1; LAMA; dyspnea; COPD
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S32451

Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD). We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.
Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout. Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment. The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.
A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV(1)] 57.1% predicted). Ninety-five patients completed the study. On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%. Dynamic IC at exercise isotime and trough FEV(1) showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study. This was accompanied by inverse decreases in residual volume and functional residual capacity. NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime). The safety profile of NVA237 was similar to that of the placebo.
NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1. This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV(1) and dyspnea. Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance. (ClinicalTrials.gov Identifier: NCT01154127).