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Background SUN-101 is a combination of glycopyrrolate delivered through an innovative, electronic nebulizer, intended for the treatment of patients with COPD. The objective of this study was to assess the efficacy and safety of this new drug device combination. Methods Replicate Phase III randomized, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of glycopyrrolate solution administered by an investigational eFlow ® Closed System (eFlow ® CS) nebulizer in subjects with moderate-to-very-severe COPD, including those with continued background use of a long-acting beta 2 -agonist ± inhaled corticosteroid and/or history of cardiovascular (CV) disease. Subjects were randomized in a 1:1:1 ratio to receive placebo or glycopyrrolate (25 μg or 50 μg twice daily [BID]) for 12 weeks. The primary efficacy endpoint was the change from baseline in trough forced expiratory volume in 1 s (FEV 1 ) at Week 12 compared with placebo. Secondary endpoints included change from baseline in forced vital capacity (FVC) after 12 weeks, change from baseline in health status measured by St George's Respiratory Questionnaire (SGRQ) at 12 weeks/end of study (EOS), and change in rescue medication use, as well as change from baseline in FEV 1 area under the curve from 0 to 12 h after 12 weeks in the GOLDEN 3 sub-study. Daytime and night-time symptoms were recorded using an electronic diary. Safety was monitored throughout the study, including major adverse cardiovascular events. Results A total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4. Treatment with glycopyrrolate 25 μg BID and 50 μg BID resulted in statistically significant and clinically important changes from baseline in trough FEV 1 compared with placebo at Week 12 (GOLDEN 3: 0.105 L and 0.126 L; p ≤ 0.0001; GOLDEN 4: 0.084 L and 0.082 L; p ≤ 0.0001). Nebulized glycopyrrolate 25 μg BID and 50 μg BID also resulted in improvements in FVC change from baseline versus placebo at Week 12 (GOLDEN 3: 0.149 L and 0.167 L, p p p p Conclusions The results of these studies demonstrated statistically significant and clinically important improvements in pulmonary function and patient-reported health outcomes, with an acceptable safety profile, support the use of glycopyrrolate/eFlow ® CS as a potential maintenance treatment for moderate-to-very-severe COPD.

Background The use of long-acting bronchodilators is an essential component of the management of chronic obstructive pulmonary disease (COPD). The GOLDEN 5 Phase III, randomized, active-controlled, open-label study was conducted to evaluate the long-term safety and tolerability of a nebulized glycopyrrolate formulation (SUN-101) delivered via the investigational eFlow® Closed System (eFlow® CS) nebulizer in subjects with moderate-to-very-severe COPD. Methods Subjects were randomized in a 4:3 ratio to nebulized glycopyrrolate 50 μg twice daily (BID) or tiotropium 18 μg once daily (OD) and treated for 48 weeks. Subjects represented the general COPD population with real-world characteristics including severe disease, presence of comorbidities, and receiving background COPD therapy. Primary endpoints were the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Secondary endpoints included the number of subjects with major adverse cardiovascular events (MACE); change from baseline in trough forced expiratory volume in 1 s (FEV1), and assessment of patient-reported outcomes. Results 1086 subjects received at least one dose of study drug. The overall incidence of TEAEs was comparable for subjects treated with glycopyrrolate (69.4%) or tiotropium (67.0%). Serious TEAEs occurred at similar rates in both treatment groups (glycopyrrolate, 12.3%; tiotropium, 10.5%). The most frequent TEAEs were COPD exacerbation/worsening and cough. Discontinuation due to TEAEs was higher in the glycopyrrolate group (10.0%) than the tiotropium group (2.8%) and related, in part, to the open-label study design, prior use of long-acting muscarinic antagonists and aerosol–airway interactions. Fewer subjects in the glycopyrrolate group experienced MACE (glycopyrrolate, n = 3 [0.5%]; tiotropium, n = 8 [1.7%]). Nebulized glycopyrrolate treatment resulted in improvements in trough FEV1 that were maintained over 48 weeks. Patient-reported health outcomes showed improvements, supporting the increases in trough FEV1. Conclusions Treatment with nebulized glycopyrrolate was well tolerated over 48 weeks with the most common adverse events being COPD worsening and cough. The overall and cardiac safety and tolerability profile and improvements in pulmonary function and patient-reported health outcomes support the use of nebulized glycopyrrolate as a maintenance treatment for moderate-to-very-severe COPD. Clinical trial registration number NCT02276222 .

SUN-101 is a combination of glycopyrrolate delivered through an innovative, electronic nebulizer, intended for the treatment of patients with COPD. The objective of this study was to assess the efficacy and safety of this new drug device combination.Replicate Phase III randomized, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of glycopyrrolate solution administered by an investigational eFlowA total of 653 subjects were randomized in GOLDEN 3 and 641 in GOLDEN 4. Treatment with glycopyrrolate 25 μg BID and 50 μg BID resulted in statistically significant and clinically important changes from baseline in trough FEVThe results of these studies demonstrated statistically significant and clinically important improvements in pulmonary function and patient-reported health outcomes, with an acceptable safety profile, support the use of glycopyrrolate/eFlow

The use of long-acting bronchodilators is an essential component of the management of chronic obstructive pulmonary disease (COPD). The GOLDEN 5 Phase III, randomized, active-controlled, open-label study was conducted to evaluate the long-term safety and tolerability of a nebulized glycopyrrolate formulation (SUN-101) delivered via the investigational eFlowSubjects were randomized in a 4:3 ratio to nebulized glycopyrrolate 50 μg twice daily (BID) or tiotropium 18 μg once daily (OD) and treated for 48 weeks. Subjects represented the general COPD population with real-world characteristics including severe disease, presence of comorbidities, and receiving background COPD therapy. Primary endpoints were the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Secondary endpoints included the number of subjects with major adverse cardiovascular events (MACE); change from baseline in trough forced expiratory volume in 1 s (FEV1086 subjects received at least one dose of study drug. The overall incidence of TEAEs was comparable for subjects treated with glycopyrrolate (69.4%) or tiotropium (67.0%). Serious TEAEs occurred at similar rates in both treatment groups (glycopyrrolate, 12.3%; tiotropium, 10.5%). The most frequent TEAEs were COPD exacerbation/worsening and cough. Discontinuation due to TEAEs was higher in the glycopyrrolate group (10.0%) than the tiotropium group (2.8%) and related, in part, to the open-label study design, prior use of long-acting muscarinic antagonists and aerosol-airway interactions. Fewer subjects in the glycopyrrolate group experienced MACE (glycopyrrolate, n = 3 [0.5%]; tiotropium, n = 8 [1.7%]). Nebulized glycopyrrolate treatment resulted in improvements in trough FEVTreatment with nebulized glycopyrrolate was well tolerated over 48 weeks with the most common adverse events being COPD worsening and cough. The overall and cardiac safety and tolerability profile and improvements in pulmonary function and patient-reported health outcomes support the use of nebulized glycopyrrolate as a maintenance treatment for moderate-to-very-severe COPD.NCT02276222.