Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial

Abstract

BackgroundNVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD). The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.MethodsPatients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled. Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry. The primary outcome measure was trough FEV1 at Week 12.ResultsA total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270). Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001). Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26. FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints. Transition dyspnoea index focal scores and St. George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively. NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo. NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.ConclusionsOnce-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.Trial registrationClinicalTrials.gov: NCT01005901

Cardiovascular safety of new inhaled medications for asthma and chronic obstructive pulmonary disease: a critical review from pharmacist perspective

“…However, GLOW 1 trail reported 3 cases of serious AF and 2 cases of congestive HF among glycopyrronium treated subjects; GLOW 2 trial observed high withdrawal rates (76% subjects completed the 52-week study), and reported 4 cases of AF, as well as transient ischemic attack and syncope among glycopyrronium groups, but no difference in mortality. 89,90 Despite similar AEs, the GLOW 7 trial observed a non-statistically significant but higher trend of mortality rate in the 26-weeks study.…”

Van-e cardiovascularis mellékhatásuk az inhalációs antikolinerg szereknek?

“…A GLOW 1-5 vizsgálatokban [24,25,26] placebo, illetve tiotropium HandiHaler kontrollja mellett szignifi káns cardiovascularis mellékhatást nem észleltek. Jelentős QT-megnyúlást sem, csak kismértékűt.…”

Addressing unmet needs in the treatment of COPD

“…Significant improvements have been observed with glycopyrronium versus placebo in lung function and clinical end-points, such as health status, dyspnoea, rescue medication use, daily symptoms, exercise endurance time and rate of exacerbations in three major clinical trials [23,[71][72][73].…”

“…Triple therapy (the combination of a LABA/LAMA with an ICS, or an ICS/LABA with a LAMA) is a treatment option for patients in GOLD group D. The improvements in lung function and clinical end-points observed with glycopyrronium [71][72][73][74] suggest that the LAMA may be a suitable candidate for use in a loose triple combination with an ICS/LABA. To study the efficacy of glycopyrronium in this approach, the GLISTEN trial investigated the efficacy (non-inferiority) of glycopyrronium compared with blinded tiotropium when added to twice-daily SFC [75].…”