Efficacy and Safety of Nebulized Glycopyrrolate/eFlow® Closed System in Patients with Moderate-to-Very-Severe Chronic Obstructive Pulmonary Disease with Pre-Existing Cardiovascular Risk Factors.

Abstract

Purpose: The purpose of this study was to assess the effect of pre-existing cardiovascular (CV) risk factors on the efficacy and safety of nebulized glycopyrrolate (GLY) in patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 2379 patients from 3 phase III studies (12-week, placebo-controlled Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer [GOLDEN] -3 and -4, and 48-week, active-controlled GOLDEN-5) stratified by high (n=1526) or low (n=853) CV risk were randomized to placebo, GLY 25 mcg or 50 mcg twice daily, or tiotropium (TIO; 18 mcg once daily). Safety, lung function, patient-reported outcomes (PROs), and exacerbations were assessed by CV risk. Results: Treatment-emergent adverse events (TEAEs) were similar across CV risk subgroups, with serious TEAEs higher in the high CV risk subgroup. In the 12-week studies, discontinuation due to TEAEs with GLY 25 mcg and 50 mcg was similar between CV risk subgroups, and lower than placebo (high risk: 6.2%, 3.6%, 9.0%; low risk: 3.2%, 4.5%, 9.9%, respectively). In the 48-week, open-label study, discontinuation rates were higher with GLY versus TIO (high risk: 10.7%, 3.7%; low risk: 8.7%, 1.2%, respectively). Rates of CV events of special interest were similar across CV risk subgroups. Regardless of CV risk, GLY led to significant improvements in efficacy and PRO assessments at 12 weeks versus placebo, whereas changes were similar between GLY and TIO at 48 weeks, except for PROs in the low risk subgroup. Exacerbation rates were similar across all treatment groups. Conclusions: Nebulized GLY had an acceptable safety profile and improved lung function and PROs in COPD patients, irrespective of CV risk status.