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 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

NCT2347761, NCT2347774.

Keywords:

• age
• COPD
• disease severity
• long-acting muscarinic antagonist
• LAMA
• nebulizer
• nebulized glycopyrrolate

Acknowledgments

The studies were funded by Sunovion Pharmaceuticals Inc. Medical writing support was provided by Linda Townsend PhD of FireKite, an Ashfield company, part of UDG Healthcare plc, and was funded by Sunovion Pharmaceuticals Inc. Aspects of these data were presented in an oral presentation: Ohar J, et al, “The efficacy and safety of a novel, nebulized glycopyrrolate for the treatment of COPD: Effect of baseline lung function and age” at the CHEST meeting, Toronto, Canada, October 28–November 1, 2017.

Author contributions

All authors had full access to the study data, conducted the analysis, and take responsibility for the integrity of the data and the accuracy of the analysis. All authors contributed to drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work. Jill Ohar contributed to data collection; Robert Tosiello contributed to study design.

Disclosure

Jill Ohar has served on advisory boards for Sunovion Pharmaceuticals Inc., AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Mylan, and Theravance, and has provided expert witness testimony for: Wallace & Graham, Levy Konigsberg, Goldenberg Heller & Antognoli, Simon Greensone Panatier Bartlett, Williams Kherkher Hart, Gori Julian & Associates, Simmons Hanley Conroy, and Elrod Pope. Robert Tosiello, Thomas Goodin, and Shahin Sanjar are employees of Sunovion Pharmaceuticals Inc. The authors report no other conflicts of interest in this work.