The Effect of Baseline Rescue Medication Use on Efficacy and Safety of Nebulized Glycopyrrolate Treatment in Patients with COPD from the GOLDEN 3 and 4 Studies

Abstract

Purpose

Rescue medication use is common in chronic obstructive pulmonary disease (COPD) patients and tends to increase with symptoms and disease severity. An analysis of baseline rescue medication use was conducted to inform on patient phenotypes and subsequent effects on lung function, symptoms, and safety following 12 weeks of nebulized glycopyrrolate (GLY) 25 µg twice daily or placebo in patients with moderate-to-very-severe COPD.

Patients and Methods

Pooled data from the 12-week, placebo-controlled GOLDEN 3 and 4 studies (n=781) were used to assign patients into quarters based on baseline rescue medication use (ie, average puffs-per-day) during the run-in period. Placebo-adjusted trough forced expiratory volume in 1 second (FEV₁), St. George’s Respiratory Questionnaire (SGRQ) total score and EXAcerbations of COPD Tool-Respiratory Symptoms (EXACT-RS) total score data were reported; safety was evaluated by reviewing the incidence of adverse events (AEs) and serious AEs (SAEs).

Results

Baseline rescue medication use was a proxy for disease severity, evidenced by decreased lung function, increased health status scores, symptom scores and use of background long-acting β2-agonists and inhaled corticosteroids across quarters and treatment groups. Treatment with GLY led to greater improvements from baseline in trough FEV₁, SGRQ and EXACT-RS scores compared with placebo in all rescue medication use quarters. Additionally, the SGRQ and EXACT-RS exhibited greater improvement with increased baseline rescue medication use with GLY treatment. In the Q4 patients, SGRQ (≥4-unit reduction) or EXACT-RS (≥2-unit reduction) responders were significantly greater with GLY compared with placebo. AE and SAE incidences were similar across quartiles.

Conclusion

These results suggest that baseline rescue medication use assessments may be useful in the management of COPD. Treatment with nebulized GLY improved lung function and symptom scores, regardless of baseline rescue medication use. These results support the use of nebulized GLY for the treatment of COPD, independent of baseline rescue medication use.

Keywords:

• COPD
• glycopyrrolate
• LAMA
• rescue medication use

View correction statement:

The Effect of Baseline Rescue Medication Use on Efficacy and Safety of Nebulized Glycopyrrolate Treatment in Patients with COPD from the GOLDEN 3 and 4 Studies [Corrigendum]

Acknowledgments

The authors would like to thank Shane Hornibrook from Sarepta Therapeutics Inc., Diane Hall from Sunovion Pharmaceuticals, Inc., and Rajeshwari Sammishetty from Sage Therapeutic, Inc., for support with statistical analyses performed. This post-hoc analysis was funded by Sunovion Pharmaceuticals, Inc. Medical writing support was provided by Hashem Dbouk, PhD, of FireKite, an Ashfield company, part of UDG Healthcare plc, and funded by Sunovion Pharmaceuticals, Inc. The abstract of this paper was presented at the American Thoracic Society 2019 International Conference as a poster with interim findings. The poster’s abstract was published in the “Abstracts Issue” of American Journal of Respiratory and Critical Care Medicine: https://doi.org/10.1164/ajrccm-conference.2019.199.1_MeetingAbstracts.A3873.

Data Sharing Statement

Sunovion Pharmaceuticals Inc. is part of a clinical trial data sharing consortium that facilitates access for qualified researchers to selected anonymized clinical trial data. For up-to-date information on data availability, please visit https://www.clinicalstudydatarequest.com/Study-Sponsors.aspx and click on Sunovion.

Disclosure

JFD has been an advisor and received personal fees from Sunovion and Mylan, and has served on advisory boards for Theravance. AO-G, TG, and SS are employees of Sunovion Pharmaceuticals, Inc. The authors report no other conflicts of interest in this work.