Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial Full Text
International Journal of COPD, 07/31/2012
Beeh KM et al. – 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 inspiratory capacity (IC) at isotime), and meaningful improvements in trough forced expiratory volume in 1 second [FEV1] and dyspnea. Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.Methods
- 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 [FEV1] 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 FEV1 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.