Trial Evaluates Effect of Nebulized Glycopyrrolate With, Without LABA in COPD

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Previous phase 3 studies have demonstrated the efficacy of nebulized glycopyrrolate inhalation solution (GLY) for treating patients with chronic obstructive pulmonary disease (COPD). In a recent study, researchers conducted a secondary analysis and found that nebulized GLY demonstrated efficacy and was well tolerated for up to 48 weeks in subjects with COPD with or without background long-acting beta₂-agonist (LABA).

The trial involved a total of 2379 subjects, who were divided among 2 12-week placebo-controlled studies (GOLDEN 3 and GOLDEN 4) and 1 48-week, open-label active-controlled study (GOLDEN 5). The patients were stratified by background LABA use and then randomized to placebo vs GLY 25 or 50 µg twice daily, or GLY 50 µg twice daily vs tiotropium (TIO) 18 µg once daily.

“Nebulized glycopyrrolate inhalation solution (GLY) is the first nebulized long-acting muscarinic antagonist (LAMA) approved in the US by the Food and Drug Administration for the treatment of patients with COPD,” the authors explained. “This analysis examines whether the continued use of another bronchodilator, a long-acting beta2 -agonist (LABA) — with or without inhaled corticosteroid (ICS) treatment – affects the efficacy and safety of nebulized GLY in patients with moderate-to-very severe COPD.”

The pooled data from the 12-week studies demonstrated significant improvements from baseline with GLY 25 and 50 µg across LABA subgroups in trough FEV₁ (lung function) and in St. George’s Respiratory Questionnaire (SGRQ) total score—which measured the health status—when compared with the placebo. Furthermore, incidence of treatment-emergent adverse events (TEAEs) was similar in LABA subgroup, and lower in GLY 25 µg compared to the placebo, according to the results.

In addition, in the 48-week active-controlled study, GLY and TIO both demonstrated improvement from baseline among LABA subgroups in FEV₁ and in the SGRQ total score. Also, the study noted that exacerbation rates were similar across treatments and LABA subgroups, while cardiovascular events of special interest were more frequent in the LABA-no subgroup.

“Following recent updates to treatment paradigms, a better understanding of the effects of LAMA, LAMA/LABA and LAMA/LABA/ICS combinations on efficacy and safety outcomes of COPD therapies may help clinicians to make informed decisions when tailoring a patient’s treatment,” the authors said. “Overall, in all three studies, SGRQ total score improvements were reported in LABA-yes and LABA-no subgroups. Based on E-RS total scores, there was a general trend toward symptom reduction across all treatment groups at end of study.”

The researchers concluded that these results could provide necessary information to clinicians who manage patients with COPD who require combination therapies to treat their disease.

Reference

Kerwin EM, Tosiello R, Price B, Sanjar S, Goodin T. Effect of background long-acting beta2-agonist therapy on the efficacy and safety of a novel, nebulized glycopyrrolate in subjects with moderate-to-very-severe COPD. [published online September 19, 2018]. Int J Chron Obstruct Pulmon Dis. doi: 10.2147/COPD.S172408