Glycopyrronium ( Seebri Breezhaler ) is a once daily long-acting muscarinic antagonist that is approved for maintenance treatment of COPD ( chronic obstructive pulmonary disease ). This post-hoc pooled analysis of two phase III studies, GLycopyrronium bromide in COPD airWays 1 and 2 ( GLOW1 and GLOW2 ), has evaluated the effects of Glycopyrronium compared with placebo and Tiotropium ( Spiriva ) over 26-52 weeks in patients with moderate-to-severe COPD.
Patients aged greater than or equal to 40 years were randomised to 26 weeks' treatment with Glycopyrronium 50 mcg once daily or placebo ( GLOW1 ) or 52 weeks' treatment with Glycopyrronium 50 mcg once daily, placebo, or open-label tiotropium 18 mcg once daily ( GLOW2 ).
The primary efficacy endpoint in both studies was trough forced expiratory volume in one second ( FEV1 ) at Week 12. Other outcomes included additional spirometry endpoints, moderate or severe exacerbations, dyspnoea, health status, rescue medication use and safety.
Serial spirometry over 24 hours was conducted in a subset of patients.
Of 1888 subjects randomised, 98.2% were analysed ( Glycopyrronium 1059, Tiotropium 267, placebo 528 ). Least squares mean ( LSM ) trough FEV1 was significantly higher with Glycopyrronium versus placebo at Week 12 ( treatment difference ± standard error [ SE ]: 103±11.2 mL; p less than 0.001 ), as well as at Day 1 and Weeks 26 and 52.
More patients achieved greater than or equal to 100 mL increase in trough FEV1 from baseline with Glycopyrronium versus placebo at all assessments ( p less than 0.001 ).
Glycopyrronium has significantly improved FEV1 immediately after the first dose on Day 1 versus placebo ( 90 mL at 5 minutes, 144 mL at 15 minutes; both p less than 0.001 ) and versus Tiotropium ( 43 mL at 5 minutes, 65 mL at 15 minutes; both p less than 0.001 ).
Glycopyrronium has significantly improved other spirometry endpoints and provided clinically meaningful 24 hour bronchodilation versus placebo at most timepoints from Day 1 onwards ( p less than 0.05 ).
Time to first moderate or severe exacerbation was significantly prolonged with Glycopyrronium versus placebo over 26 and 52 weeks ( 36% and 33%, respectively; both p less than 0.001 ).
Glycopyrronium has provided significantly greater relief of dyspnoea, improved health status and reduced rescue medication use versus placebo.
Glycopyrronium was safe and well tolerated.
In conclusion, Glycopyrronium 50 mcg once daily has provided early bronchodilation after the first dose that was sustained for 24 hours, and reduced the risk of exacerbations compared with placebo, with efficacy at least equivalent to Tiotropium. ( Xagena )
D'Urzo A et al, Curr Med Res Opin 2014;30:493-508