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

Int J Chron Obstruct Pulmon Dis. 2018 Dec 18;14:27-37. doi: 10.2147/COPD.S184808. eCollection 2019.

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 FEV1 (<50%, ≥50%) and age (<65, ≥65, ≥75 years).

Results: GLY (25 and 50 μg BID) produced significant improvements in trough FEV1 in FEV1% 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 FEV1% 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.

Keywords: COPD; LAMA; age; disease severity; long-acting muscarinic antagonist; nebulized glycopyrrolate; nebulizer.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Clinical Trials, Phase III as Topic
  • Drug Administration Schedule
  • Female
  • Forced Expiratory Volume
  • Glycopyrrolate / administration & dosage*
  • Glycopyrrolate / adverse effects
  • Health Status
  • Humans
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage*
  • Muscarinic Antagonists / adverse effects
  • Nebulizers and Vaporizers
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Randomized Controlled Trials as Topic
  • Recovery of Function
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Bronchodilator Agents
  • Muscarinic Antagonists
  • Glycopyrrolate

Associated data

  • ClinicalTrials.gov/NCT02347761
  • ClinicalTrials.gov/NCT02347774