Introduction The fundamental characteristics of COPD are exertional dyspnoea and exercise limitation, which are associated with dynamic hyperinflation. We assessed the effects of NVA237 (glycopyrronium bromide), a once-daily long-acting muscarinic antagonist (LAMA), on exercise endurance in patients with moderate-to-severe COPD.

Methods Patients with COPD were randomised to a cross-over design of NVA237 50 μg or placebo once daily for 3 weeks, with a 14-day washout. The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test (SMETT) on Day 21 of treatment. Endurance time after first dose, dynamic hyperinflation (inspiratory capacity [IC] at isotime during exercise), and morning trough FEV₁ and plethysmographic lung volumes were also measured.

Results 108 patients were randomised; mean age was 60.5 years, mean post-bronchodilator FEV₁ was 57.1% predicted. 88.0% completed the study. Endurance time on Day 21 significantly increased by 21% with NVA237 vs placebo; the effect was significant from Day 1, with an increase of 10%. Both dynamic IC at exercise isotime and trough FEV₁ showed significant and clinically relevant improvements from Day 1 that were maintained for the study duration (Abstract P254 table 1). This was accompanied by inverse decreases in residual volume and functional residual capacity (Abstract P254 table 1). Overall, the safety profile of NVA237 was similar to that of placebo.

Conclusion Once-daily NVA237 provided immediate and significant improvement in exercise endurance from Day 1. This was accompanied by sustained and significant improvements in IC at isotime, meaningful improvements in trough FEV₁, and sustained reductions of lung hyperinflation. There was an improvement in endurance time during the study period, suggesting that mechanisms beyond improved lung function play a part in superior exercise tolerance.