Efficacy and safety of a novel, nebulized glycopyrrolate for the treatment of COPD: Effect of baseline disease severity and age; pooled analysis of GOLDEN 3 and GOLDEN 4

Abstract

Background: The efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY), administered twice daily (BID) via the innovative eFlow® Closed System nebulizer (PARI Pharma GmbH, Starnberg, Germany), were demonstrated in two replicate, placebo-controlled, 12-week Phase III studies (GOLDEN 3 and GOLDEN 4). This report evaluates the efficacy and safety of GLY by baseline disease severity and age in the pooled GOLDEN 3 and GOLDEN 4 patient population (N=1,294). Methods: Patients were grouped by baseline predicted post-bronchodilator FEV 1 (,50%, $50%) and age (,65, $65, $75 years). Results: GLY (25 and 50 μg BID) produced significant improvements in trough FEV 1 in FEV 1 % predicted,50% (0.070 L, 0.079 L) and $50% (0.112 L, 0.126 L) subgroups (P,0.01 vs placebo), and in patients aged,65 (0.056 L, 0.086 L), $65 (0.140 L, 0.124 L), and $75 (0.144 L, 0.120 L) years (P,0.05 vs placebo). St George’s Respiratory Questionnaire (SGRQ) total score was significantly improved with GLY 25 and 50 μg BID (P,0.05 vs placebo) in FEV 1 % predicted,50% (-3.237,-3.061) and $50% (-3.392,-2.322) and in,65 years (-3.447,-2.318) and $65 years (-3.053,-3.098) subgroups. In patients aged $75 years, GLY 25 μg reduced SGRQ total score by-6.278 units (P,0.01 vs placebo). The incidence of treatment-emergent adverse events was similar between GLY and placebo across all subgroups, and the overall incidence of cardiovascular events was low. Conclusions: Nebulized GLY improved lung function and health status and was well tolerated over 12 weeks in patients with moderate-to-very-severe COPD, irrespective of baseline disease severity and age. Clinical trial registration: NCT02347761, NCT02347774.