Efficacy and safety of coadministration of once-daily indacaterol and glycopyrronium versus indacaterol alone in COPD patients: the GLOW6 study
Walter Vincken, Joseph Aumann, Hungta Chen, Michelle Henley, Danny McBryan, Pankaj Goyal, Walter Vincken, Joseph Aumann, Hungta Chen, Michelle Henley, Danny McBryan, Pankaj Goyal
Abstract
Background: Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.
Materials and methods: In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices). The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.
Results: A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001). IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01). TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05). The incidence of adverse events was similar for the two treatment groups.
Conclusion: In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.
Trial registration: ClinicalTrials.gov NCT01604278.
Keywords: Breezhaler®; COPD; bronchodilation; glycopyrronium; indacaterol; inhalation therapy.
Figures
References
- Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. [Accessed on January 8, 2014]. Available from:
- Cazzola M, Matera MG. Long-acting bronchodilators are the first-choice option for the treatment of stable COPD. Chest. 2004;125(1):9–11.
- European Medicines Agency (EMA) Seebri Breezhaler (glycopyrronium bromide: summary of product characteristics. [Accessed June 25, 2013]. Available from: .
- Novartis Global . Novartis receives European Commission approval for once-daily Seebri® Breezhaler® as maintenance COPD treatment in the EU [press release] Basel, Switzerland: Novartis; 2012. [Accessed 22 November, 2012]. [October 1]. Available from: .
- European Medicines Agency (EMA) Bretaris Genuair (aclidinium bromide): summary of product characteristics. [Accessed June 25, 2013]. Available from: .
- European Medicines Agency (EMA) Eklira Genuair (aclidinium bromide): summary of product characteristics. [Accessed June 25, 2013]. Available from: .
- US Food and Drug Administration (FDA) Tudorza Pressair (aclidinium bromide): US prescribing information. [Accessed June 25, 2013]. Available from: .
- Beeh KM, Singh D, Di SL, Drollmann A. Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial. Int J Chron Obstruct Pulmon Dis. 2012;7:503–513.
- Chapman KR, Rennard SI, Dogra A, Owen R, Lassen C, Kramer B. Long-term safety and efficacy of indacaterol, a long-acting β2-agonist, in subjects with COPD: a randomized, placebo-controlled study. Chest. 2011;140(1):68–75.
- 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.
- Dahl R, Chung KF, Buhl R, et al. Efficacy of a new once-daily long-acting inhaled beta2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax. 2010;65(6):473–479.
- Donohue JF, Fogarty C, Lötvall J, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med. 2010;182(2):155–162.
- Kerwin E, Hébert 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(5):1106–1114.
- Kornmann O, Dahl R, Centanni S, et al. Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison. Eur Respir J. 2011;37(2):273–279.
- Korn S, Kerwin E, Atis S, Amos C, Owen R, Lassen C. Indacaterol once-daily provides superior efficacy to salmeterol twice-daily in COPD: a 12-week study. Respir Med. 2011;105(5):719–726.
- Buhl R, Dunn LJ, Disdier C, et al. Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD. Eur Respir J. 2011;38(4):797–803.
- Vogelmeier C, Ramos-Barbon D, Jack D, et al. Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison with tiotropium. Respir Res. 2010;11:135.
- van Noord JA, Aumann JL, Janssens E, et al. Combining tiotropium and salmeterol in COPD: effects on airflow obstruction and symptoms. Respir Med. 2010;104(7):995–1004.
- Vincken W. An update of bronchodilator treatment of chronic obstructive pulmonary disease (COPD) [abstract] Ann Respir Med. 2010;1:1–16.
- Vogelmeier C, Kardos P, Harari S, Gans SJ, Stenglein S, Thirlwell J. Formoterol mono- and combination therapy with tiotropium in patients with COPD: a 6-month study. Respir Med. 2008;102(11):1511–1520.
- Mahler DA, D’Urzo A, Bateman ED, et al. Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison. Thorax. 2012;67(9):781–788.
- Maltais F, Beck E, Webster D, et al. Four weeks once daily treatment with tiotropium + olodaterol (BI 1744) fixed dose combination compared with tiotropium in COPD patients [abstract] Eur Respir J. 2010;36:5557.
- Tashkin DP, Littner M, Andrews CP, Tomlinson L, Rinehart M, Denis-Mize K. Concomitant treatment with nebulized formoterol and tiotropium in subjects with COPD: a placebo-controlled trial. Respir Med. 2008;102(4):479–487.
- Tashkin DP, Pearle J, Iezzoni D, Varghese ST. Formoterol and tiotropium compared with tiotropium alone for treatment of COPD. COPD. 2009;6(1):17–25.
- van Noord JA, Aumann JL, Janssens E, et al. Effects of tiotropium with and without formoterol on airflow obstruction and resting hyperinflation in patients with COPD. Chest. 2006;129(3):509–517.
- van Noord JA, Aumann JL, Janssens E, et al. Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD. Eur Respir J. 2005;26(2):214–222.
- Bateman ED, Ferguson GT, Barnes N, et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J. 2013 Dec;42(6):1484–1494.
- Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2010. [Accessed November 23, 2013]. Available from:
- identifier NCT01604278. [Accessed on 16th January 2014]. .
- Mozzicato P, MedDRA An Overview of the Medical Dictionary for Regulatory Activities. Pharm Med. 2009;23:65–75.
- Witek TJ, Jr, Mahler DA. Minimal important difference of the transition dyspnoea index in a multinational clinical trial. Eur Respir J. 2003;21(2):267–272.
- Jones PW. St George’s Respiratory Questionnaire: MCID. COPD. 2005;2(1):75–79.
- In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. An 85-day multicenter trial. COMBIVENT Inhalation Aerosol Study Group. Chest. 1994;105(5):1411–1419. [No authors listed]
- Routine nebulized ipratropium and albuterol together are better than either alone in COPD. The COMBIVENT Inhalation Solution Study Group. Chest. 1997;112(6):1514–1521. [No authors listed]
- Mahler DA, Decramer M, D’Urzo A, et al. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: BLAZE study. Eur Respir J. 2013 Oct 31; [Epub ahead of print]
- Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19(2):217–224.
- Yawn BP, Kaplan A. Co-morbidities in people with COPD: a result of multiple diseases, or multiple manifestations of smoking and reactive inflammation? Prim Care Respir J. 2008;17(4):199–205.
- Calverley PM, Rennard SI. What have we learned from large drug treatment trials in COPD? Lancet. 2007;370(9589):774–785.
- Decramer M, Celli B, Kesten S, Lystig T, Mehra S, Tashkin DP. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet. 2009;374(9696):1171–1178.
- Vincken W, van Noord JA, Greefhorst AP, et al. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J. 2002;19(2):209–216.
- Vogelmeier C, Bateman E, Pallante J, et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol – fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study. Lancet Respir Med. 2013;1(1):51–60.
- Price D, Yawn B, Brusselle G, Rossi A. Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD. Prim Care Respir J. 2013;22(1):92–100.
Source: PubMed