Efficacy and safety of glycopyrrolate/eFlow® CS (nebulized glycopyrrolate) in moderate-to-very-severe COPD: Results from the glycopyrrolate for obstructive lung disease via electronic nebulizer (GOLDEN) 3 and 4 randomized controlled trials

Kerwin, Edward; Donohue, James F.; Goodin, Thomas; Tosiello, Robert; Wheeler, Alistair; Ferguson, Gary T.

doi:10.1016/j.rmed.2017.07.011

Cited by 39 publications

(93 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Details of the GOLDEN 3 and GOLDEN 4 studies have been previously described ( Figure 1). 7 Briefly, in the 12-week, multicenter, placebo-controlled, double-blind studies, subjects (N=1293) were randomized in a 1:1:1 ratio and received placebo or GLY (25 or 50 µg BID), via the eFlow CS Nebulizer; 781 patients who received either GLY 25 µg BID or placebo and had baseline rescue medication use data available are included in this analysis. Randomization in each of the studies was stratified by background long-acting beta 2 -agonist (LABA) use (yes/no) and by cardiovascular (CV) risk (high/low).…”

Section: Methodsmentioning

confidence: 99%

“…, randomized, double-blind, placebo-controlled, parallel-group, multicenter studies. 7 Notes: a SAEs were monitored for 30 days after the last dose of study treatment; b Data for the GLY 50 µg BID treatment arm are not presented in this post-hoc analysis but were used in the modeling and in defining the rescue medication subgroups studied in this analysis; inclusion of the 50 µg BID data in the modeling does not confound the interpretation of the GLY 25 µg BID dose. Abbreviations: BID, twice daily; CS, closed system; GLY, nebulized glycopyrrolate; GOLDEN, Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer; ICS, inhaled corticosteroids; LABA, long-acting beta 2 -agonist; min, minimum; SAE, serious adverse event; tx, treatment.…”

Section: Methodsmentioning

confidence: 99%

“…Detailed patient inclusion and exclusion criteria have been published previously. 7 Briefly, enrolled patients included males or females ≥40 years of age, current or ex-smokers with ≥10 pack-year smoking history, a clinical diagnosis of moderate-to-very-severe COPD (as defined by the GOLD 2014 Report 8 ), and qualifying post-bronchodilator (ipratropium 68 µg) spirometry (FEV 1 ≤80% of predicted normal, FEV 1 >0.7 L, and FEV 1 /forced vital capacity ratio [FVC] <0.70). 7…”

Section: Patientsmentioning

confidence: 99%

“…Safety data were analyzed using descriptive statistics. 7 Adverse events (AEs) and serious adverse events (SAEs) were coded according to MedDRA v15.1 and summarized by treatment, system organ class, and preferred term.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…6 Data from the 12-week, placebocontrolled Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer (GOLDEN) 3 and GOLDEN 4 Phase III studies (NCT02347761 and NCT02347774, respectively) demonstrated statistically significant and clinically important improvements in pulmonary function and patient-reported outcomes (PROs) with GLY compared with placebo in patients with moderate-to-very-severe COPD. 7 In this analysis of pooled data from the 12-week GOLDEN 3 and GOLDEN 4 studies, we assessed the impact of baseline rescue medication use on patient's physiologic and symptomatic responses to nebulized GLY compared with placebo.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

<p>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</p>

Donohue

Ozol-Godfrey

Goodin

et al. 2020

COPD

Self Cite

View full text Add to dashboard Cite

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-tovery-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 (FEV 1), 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 FEV 1 , 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.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

<p>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</p>

Donohue

Ozol-Godfrey

Goodin

et al. 2020

COPD

Self Cite

View full text Add to dashboard Cite

show abstract

Efficacy of Nebulized Glycopyrrolate on Lung Hyperinflation in Patients with COPD

et al. 2021

View full text Add to dashboard Cite

Introduction Lung hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with activity limitation, impaired cardiac output, and mortality. Several studies have demonstrated that long-acting muscarinic antagonists (LAMAs) delivered by dry powder inhalers can promote lung deflation; however, the potential of nebulized LAMAs on improving hyperinflation in COPD is currently unknown. Methods This single-center, randomized, double-blind, two-way crossover study (NCT04155047) evaluated the efficacy of a single dose of nebulized LAMA [glycopyrrolate (GLY) 25 µg] versus placebo in patients with COPD and lung hyperinflation. Patients with moderate-to-severe COPD and a residual volume (RV) ≥ 130% of predicted normal were included. The primary endpoint was changed from baseline in RV at 6 h post-treatment. Other endpoints included changes from baseline in spirometric and plethysmographic measures up to 6 h post-treatment. Results A total of 22 patients (mean pre-bronchodilator RV, 153.7% of predicted normal) were included. The primary objective of the study was not met; the placebo-adjusted least squares (LS) mean [95% confidence interval (CI) change from baseline in RV with GLY at 6 h post-treatment was − 0.323 l (− 0.711 to 0.066); p = 0.0987]. A post hoc evaluation of the primary analysis was conducted after excluding a single statistical outlier; substantial improvements in RV with GLY compared with placebo was observed after exclusion of this outlier [placebo-adjusted LS mean change from baseline (95% CI) in RV was − 0.446 l (− 0.741 to − 0.150)]. Improvements from baseline were also observed with GLY compared with placebo in spirometric and plethysmographic measures up to 6 h post-treatment. GLY was generally safe, and no new safety signals were detected. Conclusions This is the first study to evaluate the effect of nebulized GLY on lung deflation. Nebulized GLY resulted in marked improvements in RV up to 6 h post-treatment, compared with placebo. Improvements were also observed with GLY in spirometric and plethysmographic parameters of lung function. Trial Registration ClinicalTrials.gov identifier, NCT04155047. Supplementary Information The online version contains supplementary material available at 10.1007/s41030-021-00166-5.

show abstract

Pharmacokinetics, pharmacodynamics and safety of a novel extrafine BDP/FF/GB combination delivered via metered-dose inhaler in healthy Chinese subjects

Miao

Shu

et al. 2020

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Efficacy and safety of glycopyrrolate/eFlow® CS (nebulized glycopyrrolate) in moderate-to-very-severe COPD: Results from the glycopyrrolate for obstructive lung disease via electronic nebulizer (GOLDEN) 3 and 4 randomized controlled trials

Cited by 39 publications

References 29 publications

<p>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</p>

<p>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</p>

Efficacy of Nebulized Glycopyrrolate on Lung Hyperinflation in Patients with COPD

Pharmacokinetics, pharmacodynamics and safety of a novel extrafine BDP/FF/GB combination delivered via metered-dose inhaler in healthy Chinese subjects

Contact Info

Product

Resources

About