Yimeng Lu

Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study

NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD). The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks. Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks. Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks. 1,066 patients were randomised, 810 completed the study. At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6–130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6–121.4; p<0.001). Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St Georges Respiratory Questionnaire at week 52; p<0.001). NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo. NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes. Safety profiles were similar across groups. NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium. NVA237 can potentially be an alternative choice of LAMA for COPD patients.

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

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. Georges 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

P252 Once-daily NVA237 improves symptoms, and reduces COPD exacerbations and associated hospitalisations: the GLOW1 trial

Introduction Symptoms profoundly impact daily life of COPD patients. We assessed the influence of the once-daily (qd) long-acting muscarinic antagonist (LAMA) NVA237 (glycopyrronium bromide) on symptoms and exacerbations in patients with moderate-to-severe COPD. Methods Patients were randomised (2:1) to 26 weeks double-blind treatment with NVA237 50 μg qd or placebo (PBO) via a single-dose dry powder inhaler (Breezhaler® device). Efficacy was assessed by bronchodilation (trough FEV1 at Week 12), breathlessness on the transition dyspnoea index (TDI), HRQoL via the St. Georges Respiratory Questionnaire (SGRQ), and rescue medication use. The effect on COPD exacerbations and related hospitalisations was also assessed. Results 822 patients were randomised; 80.5% completed. NVA237 significantly increased total TDI focal score vs PBO at Week 26 (difference 1.04, 95% CI 0.583 to 1.504; p<0.0001); exceeding the minimum clinically important difference ([MCID] =1 point). Significantly more patients achieved MCID in TDI score with NVA237 (61.3% vs 48.3%; OR 1.74, 95% CI 1.249 to 2.415; p=0.001). SGRQ total score was significantly reduced with NVA237 (−2.81; p=0.004); % of patients achieving a clinically meaningful improvement in SGRQ (=4 point reduction) was significantly higher with NVA237 (56.8% vs 46.3%; OR 1.58, 95% CI 1.138 to 2.196; p=0.006). NVA237 significantly reduced rescue medication use at Week 26 (−0.46 puffs/day, p=0.005). NVA237 significantly prolonged time to first moderate/severe COPD exacerbation by 31% (HR 0.69, 95% CI 0.50 to 0.949; p=0.023) and time to first severe COPD exacerbation necessitating hospitalisation (HR 0.35, 95% CI 0.141 to 0.857; p=0.022). NVA237 significantly reduced hospitalisations due to COPD exacerbation (OR 0.34; p=0.024). Conclusion Once-daily NVA237 provided significant improvements in dyspnoea and SGRQ total score, with lower rescue medication use, and reduced risk of exacerbation and associated hospitalisations vs PBO.