A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD
Tara Rheault, Sanjeev Khindri, Mitra Vahdati-Bolouri, Alison Church, William A Fahy, Tara Rheault, Sanjeev Khindri, Mitra Vahdati-Bolouri, Alison Church, William A Fahy
Abstract
This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population. Other endpoints included: weighted mean FEV1 over 0-24 h and patient-reported outcomes (transition dyspnoea index score and St George's Respiratory Questionnaire total score). Adverse events were also assessed. A total of 1037 patients were randomised to treatment. Umeclidinium was non-inferior (margin: -50 mL) to glycopyrronium (trough FEV1 at day 85 treatment difference: 24 mL, 95% confidence intervals: -5-54). Improvements in other endpoints were similar between treatments. Adverse event incidences were similar for umeclidinium (37%) and glycopyrronium (36%). Once-daily umeclidinium was non-inferior to once-daily glycopyrronium in patients with chronic obstructive pulmonary disease in trough FEV1 at day 85. Patient-reported outcomes and safety profiles were similar for both treatments.
Conflict of interest statement
can be found alongside this article at openres.ersjournals.com
Figures
References
- Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2015. Date last updated: 2015. Date last accessed: August 10, 2015.
- Boehringer-Ingelheim. SPIRIVA. Prescribing Information. Date last updated: 2014. Date last accessed: September 3, 2015.
- Novartis. Seebri Breezhaler. Summary of product characteristics. Date last updated: 2015. Date last accessed: September 5, 2015.
- Novartis. Seebri Neohaler. Prescribing information. Date last updated: 2015. Date last accessed: November 6, 2015.
- GlaxoSmithKline. INCRUSE. Summary of product characteristics. Date last updated: 2015. Date last accessed: September 3, 2015.
- GlaxoSmithKline. INCRUSE. Prescribing information. Date last updated: 2014. Date last accessed: September 3, 2015.
- AstraZeneca. Eklira Genuair. Summary of product characteristics. Date last updated: 2015. Date last accessed: September 9, 2015.
- Almirall. Tudorza Pressair. Prescribing information. Date last updated: 2012. Date last accessed: October 28, 2015.
- Boehringer-Ingelheim. SPIRIVA. Summary of product characteristics. . Date last updated: 2014. Date last accessed: October 29, 2015.
- Chapman KR, Beeh KM, Beier J, et al. . A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study. BMC Pulm Med 2014; 14: 4.
- Riario-Sforza GG, Ridolo E, Riario-Sforza E, et al. . Glycopyrronium bromide for the treatment of chronic obstructive pulmonary disease. Expert Rev Respir Med 2015; 9: 23–33.
- Cope S, Donohue JF, Jansen JP, et al. . Comparative efficacy of long-acting bronchodilators for COPD: a network meta-analysis. Respir Res 2013; 14: 100.
- Karabis A, Lindner L, Mocarski M, et al. . Comparative efficacy of aclidinium versus glycopyrronium and tiotropium, as maintenance treatment of moderate to severe COPD patients: a systematic review and network meta-analysis. Int J Chron Obstruct Pulmon Dis 2013; 8: 405–423.
- Ismaila AS, Huisman EL, Punekar YS, et al. . Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis. Int J Chron Obstruct Pulmon Dis 2015; 10: 2495–2517.
- Segreti A, Calzetta L, Rogliani P, et al. . Umeclidinium for the treatment of chronic obstructive pulmonary disease. Expert Rev Respir Med 2014; 8: 665–671.
- Donohue JF, Anzueto A, Brooks J, et al. . A randomized, double-blind dose-ranging study of the novel LAMA GSK573719 in patients with COPD. Respir Med 2012; 106: 970–979.
- Trivedi R, Richard N, Mehta R, et al. . Umeclidinium in patients with COPD: a randomised, placebo-controlled study. Eur Respir J 2014; 43: 72–81.
- D'Urzo A, Ferguson GT, van Noord JA, et al. . Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial. Respir Res 2011; 12: 156.
- Fogarty C, Hattersley H, Di Scala L, et al. . Bronchodilatory effects of NVA237, a once daily long-acting muscarinic antagonist, in COPD patients. Respir Med 2011; 105: 337–342.
- Kerwin E, Hebert J, Gallagher N, et al. . Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study. Eur Respir J 2012; 40: 1106–1114.
- Celli BR, MacNee W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004; 23: 932–946.
- Mahler DA, Witek TJ Jr. The MCID of the transition dyspnea index is a total score of one unit. COPD 2005; 2: 99–103.
- Jones PW. St. George's Respiratory Questionnaire: MCID. COPD 2005; 2: 75–79.
- Kon SS, Canavan JL, Jones SE, et al. . Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir Med 2014; 2: 195–203.
- Donohue JF. Minimal clinically important differences in COPD lung function. COPD 2005; 2: 111–124.
- Snapinn SM. Noninferiority trials. Curr Control Trials Cardiovasc Med 2000; 1: 19–21.
- Lewis JA, Machin D. Intention to treat: who should use ITT? Br J Cancer 1993; 68: 647–650.
- Witek TJ Jr, Mahler DA. Meaningful effect size and patterns of response of the transition dyspnea index. J Clin Epidemiol 2003; 56: 248–255.
- Witek TJ Jr, Mahler DA. Minimal important difference of the transition dyspnoea index in a multinational clinical trial. Eur Respir J 2003; 21: 267–272.
- Jones PW, Harding G, Berry P, et al. . Development and first validation of the COPD Assessment Test. Eur Respir J 2009; 34: 648–654.
- Rennard S, Fogarty C, Reisner C, et al. . Randomized study of the safety, pharmacokinetics, and bronchodilatory efficacy of a proprietary glycopyrronium metered-dose inhaler in study patients with chronic obstructive pulmonary disease. BMC Pulm Med 2014; 14: 118.
Source: PubMed