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Inhaled Umeclidinium in COPD Patients: A Review and Meta-Analysis

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Abstract

A number of new agents for the management of chronic obstructive pulmonary disease (COPD) are at different stages of development, including several inhaled long-acting antimuscarinics (LAMA). Long-acting bronchodilators are considered to be central to the management of COPD due to the evidence supporting their efficacy and safety. Umeclidinium, a LAMA, has recently been approved for the maintenance treatment of moderate to very severe COPD in a number of countries. This comprehensive review and pooled meta-analysis provides detailed information about the efficacy and safety of this agent. The pharmacokinetics and pharmacodynamics of umeclidinium observed in phase I and II studies support its once-daily administration. Umeclidinium is rapidly cleared from blood, and renal or hepatic impairment do not lead to significant changes in drug disposition. A pooled analysis of phase III and comparative studies of umeclidinium in patients with moderate to very severe COPD showed significant improvement in lung function measures, including trough forced expiratory volume in 1 s (FEV1), as well as in acute exacerbations of COPD, dyspnea, and quality of life. Adverse effects, including known anticholinergic effects, were uncommon with umeclidinium. Limited data suggest the efficacy of umeclidinium is similar to that of tiotropium. Umeclidinium is administered as a dry powder inhaler, provides adequate lung delivery in patients with moderate to very severe airflow obstruction, and appears to be easily used by patients. Umeclidinium provides a safe and effective option as an inhaled LAMA for the management of COPD.

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References

  1. Global initiative for Chronic Obstructive Lung Disease: global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2015. Available from: http://www.goldcopd.org/. Accessed 14 Feb 2015.

  2. Church A, Beerahee M, Brooks J, Mehta R, Shah P. Dose response of umeclidinium administered once or twice daily in patients with COPD: a randomised cross-over study. BMC Pulm Med. 2014;14:2.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Tal-Singer R, Cahn A, Mehta R, Preece A, Crater G, Kelleher D, Pouliquen I. Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies. Eur J Pharmacol. 2013;701:40–8.

    Article  CAS  PubMed  Google Scholar 

  4. Kesler B, Canning B. Regulation of baseline cholinergic tone in guinea pig airway smooth muscle. J Physiol. 1999;518:843–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Barnes P. Distribution of receptor targets in the lung. Proc Am Thorac Soc. 2004;1:345–51.

    Article  CAS  PubMed  Google Scholar 

  6. Canning BJ, Fisher A. Neural regulation of airway smooth muscle tone. Respir Physiol. 2001;125:113–27.

    Article  CAS  PubMed  Google Scholar 

  7. Coulson FR, Fryer AD. Muscarinic ACh receptors and airway diseases. Pharmacol Ther. 2003;98:59–69.

    Article  CAS  PubMed  Google Scholar 

  8. Belmonte KE. Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2:297–304.

    Article  CAS  PubMed  Google Scholar 

  9. Rhoden KJ, Meldrum LA, Barnes P. Inhibition of cholinergic transmission in human airways by B2-receptors. J Appl Physiol. 1988;65:700–7.

    CAS  PubMed  Google Scholar 

  10. Salmon M, Luttman MA, Foley JJ, Buckley PT, Schmidt DB, Burman M, et al. Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013;345:260–70.

    Article  CAS  PubMed  Google Scholar 

  11. Cazzola M, Page CP, Calzetta L, Matera MG. Pharmacology and therapeutics of bronchodilators. Pharmacol Rev. 2012;64:450–504.

    Article  CAS  PubMed  Google Scholar 

  12. Yohannes AM, Connolly MJ, Hanania NA. Ten years of tiotropium: clinical impact and patient perspectives. Int J COPD. 2013;8:117–25.

    Article  CAS  Google Scholar 

  13. Bateman ED, Rennard S, Barnes PJ, Dicpinigaitis PV, Gosens R, et al. Alternative mechanisms for tiotropium. Pulm Pharmacol Ther. 2009;22:533–42.

    Article  CAS  PubMed  Google Scholar 

  14. Cahn A, Mehta R, Preece A, Blowers J, Dona A. Safety, tolerability and pharmacokinetics and pharmacodynamics of inhaled once-daily umeclidinium in healthy adults deficient in CYP2D6 activity: a double-blind, randomized clinical trial. Clin Drug Investig. 2013;33:653–64.

    Article  CAS  PubMed  Google Scholar 

  15. Hu C, Jia J, Dong K, Luo L, Kai K, et al. Pharmacokinetics and tolerability of inhaled umeclidinium and vilanterol alone and in combination in healthy Chinese subjects: a randomized, open-label, crossover trial. PLoS One. 2015;10(3):e0121264.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Cahn A, Tal-Singer R, Pouliquen J, Mehta R, Preece A, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat inhaled doses of umeclidinium in healthy subjects: two randomized studies. Clin Drug Investig. 2013;33:477–88.

    Article  CAS  PubMed  Google Scholar 

  17. Kelleher DL, Mehta R, Jean-Francois BM, Preece AF, Blowers J, et al. Safety, tolerability, pharmacodynamics and pharmacokinetics of umeclidinium and vilanterol alone and in combination: a randomized crossover trial. PLoS One. 2012;7(12):e50716.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. GSK [data on file]. NCT 01362257 An open-label, two-period study to determine the excretion balance and pharmacokinetics of [14C]-GSK573719 in humans administered as a single dose of an oral solution and an intravenous infusion, to healthy male subjects. http://www.clinicaltrials.gov.

  19. GSK [data on file]. NCT01110018 A single-centre, open-label, sequential, crossover study to examine the safety, tolerability and pharmacokinetics of three ascending single intravenous doses, a single 1000 mcg oral dose and a single 1000 mcg inhaled dose of GSK 573719 in healthy male volunteers. http://www.clinicaltrials.gov.

  20. Mehta R, Kelleher D, Preece A, Hughes S, Crater G. Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study. Int J COPD. 2013;8:159–67.

    Article  CAS  Google Scholar 

  21. Mehta R, Hardes D, Kelleher D, Preece A, Tombs L, Brealey N. Clinical effects of moderate hepatic impairment on the pharmacokinetic properties and tolerability of umeclidinium and vilanterol in inhalational umeclidinium monotherapy and umeclidinium/vilanterol combination therapy: an open-label, nonrandomized study. Clin Ther. 2014;36:1016–27.e.2.

  22. Mehta R, Hardes K, Brealey N, Tombs L, Preece A, Kelleher D. Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study. Int J COPD. 2015;10:15–23.

    Google Scholar 

  23. Laine´ DI, Luttmann MA, Foley JJ, Dehaas CJ, Kotzer CJ, Salmon M, Rumsey WL. The pre-clinical pharmacology of the inhaled muscarinic antagonist GSK573719 predicts once-daily clinical dosing. Eur Respir J. 2011;38(Suppl 5):613s [abstract].

  24. Ortiz S, Flach S, Ho J, Li F, Caracta CF, Gil EG, Jansat JM. Mass balance and metabolism of aclidinium bromide following intravenous administration of (14C)-aclidinium bromide in healthy subjects. Biopharm Drug Dispos. 2012;33:39–45.

    Article  CAS  PubMed  Google Scholar 

  25. Decramer M, Maltais F, Feldman G, Brooks J, Harrise S, Mehta R. Bronchodilation of umeclidinium, a new long-acting muscarinic antagonist, in COPD patients. Respir Physiol Neurobiol. 2013;185:393–9.

    Article  CAS  PubMed  Google Scholar 

  26. Kelleher D, Tombs L, Preece A c, Brealey N, Mehta R. A randomized, placebo- and moxifloxacin-controlled thorough QT study of umeclidinium monotherapy and umeclidinium/vilanterol combination in healthy subjects. Pulm Pharmacol Ther. 2014;29;49e57.

  27. Goyal N, Beerahee M, Kalberg C, Church A, Kilbride S, Mehta R. Population pharmacokinetics of inhaled umeclidinium and vilanterol in patients with chronic obstructive pulmonary disease. Clin Pharmacokinet. 2014;53:637–48.

    Article  CAS  PubMed  Google Scholar 

  28. 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;106:970e979.

  29. Donohue JF, Kalberg C, Shah P, Beerahe M, Mehta R. Dose response of umeclidinium administered once or twice daily in patients with COPD: a pooled analysis of two randomized, double-blind, placebo-controlled studies. J Clin Pharmacol. 2014;54(11):1214–20.

    Article  CAS  PubMed  Google Scholar 

  30. Higgins JP, Green S (eds). Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: http://handbook.cochrane.org. Accessed 15 Apr 2015.

  31. Trivedi R, Richard N, Mehta R, Church A. Umeclidinium in patients with COPD: a randomised, placebo-controlled study. Eur Respir J. 2014;43:72–81.

    Article  CAS  PubMed  Google Scholar 

  32. Celli B, Crater G, Kilbride S, Mehta R, Tabberer M, et al. Once-daily umeclidinium/vilanterol 125/25 mg therapy in COPD a randomized, controlled study. Chest. 2014;145:981–91.

    Article  CAS  PubMed  Google Scholar 

  33. Maltais F, Singh S, Donald A, et al. Effects of a combination of umeclidinium/vilanterol on exercise endurance in patients with chronic obstructive pulmonary disease: two randomized, double-blind clinical trials. Ther Adv Resp Dis. 2014;8:169–81.

    Article  Google Scholar 

  34. Siler TM, Kerwin E, Sousa AR, et al. Efficacy and safety of umeclidinium added to fluticasone furoate/vilanterol in chronic obstructive pulmonary disease: results of two randomized studies. Respir Med. 2015;109:1155–63.

    Article  PubMed  Google Scholar 

  35. Decramer M, Anzueto A, Kerwin E, Kaelin T, Richard N, Crater G, et al. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med. 2014;2:472–86.

    Article  CAS  PubMed  Google Scholar 

  36. Donohue JF, Maleki-Yazdi MR, Kilbride S, Mehta R, Kalberg C, Church A. Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Respir Med. 2013;107:1538e1546.

  37. Donohue JF, Niewoehner D, Brooks J, O’Dell D, Church A. Safety and tolerability of once-daily umeclidinium/vilanterol 125/25 mcg and umeclidinium 125 mcg in patients with chronic obstructive pulmonary disease: results from a 52-week, randomized, double-blind, placebo-controlled study. Respir Res. 2014;15:78.

    PubMed Central  PubMed  Google Scholar 

  38. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Sterne J, Egger M, Moher D. Addressing reporting biases. In: Higgins JP, Green S (eds). Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: http://handbook.cochrane.org. Accessed 15 Apr 2015.

  40. Littell J, Corcoran J, Pillai V. Systematic review and meta-analysis. New York: Oxford University Press; 2008.

    Book  Google Scholar 

  41. Deeks J, Higgins J, Altman D. Analysing data and undertaking meta-analyses. In: Higgins JP, Green S (eds). Cochrane handbook for systematic reviews of interventions. Version 5.1.0. [updated March 2011]. The Cochrane Collaboration, 2011. Available from: http://www.cochrane-handbook.org. Accessed 15 April 2015.

  42. Grant AC, Walker R, Hamilton M, Garrill K. The ELLIPTA® dry powder inhaler: design, functionality, in vitro dosing performance and critical task compliance by patients and caregivers. J Aerosol Med Pulm Drug Deliv. 2015;28(6):474–85.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Hamilton M, Leggett R, Pang C, Charles S, Gillett B, Prime D. In vitro performance of Ellipta® dry powder inhaler using asthma and COPD patient inhalation profiles replicated with then electronic lung (eLung®). J Aerosol Med Pulm Drug Deliv. 2015;28(6):498–506.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. GSK [data on file]. N211360.

  45. Hoppentocht M, Hagedoorn P, Frijlink HW, de Boer AH. Technological and practical challenges of dry powder inhalers and formulations. Adv Drug Deliv Rev. 2014;75:18–31.

    Article  CAS  PubMed  Google Scholar 

  46. Prime D, De Backer W, Hamilton M, et al. Effect of disease severity in asthma and chronic obstructive pulmonary disease on inhaler-specific inhalational profiles through the ELLIPTA® dry powder inhaler. J Aerosol Med Pulm Drug Deliv. 2015;28(6):486–97.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Svedsater H, Jacques L, Goldfrad C, Bleecker ER. Ease of use of the ELLIPTA dry powder inhaler: data from three randomised controlled trials in patients with asthma. NPJ Prim Care Respir Med. 2014;24:14019.

    PubMed Central  PubMed  Google Scholar 

  48. Komase Y, Asako A, Kobayashi A, Sharma R. Ease-of-use preference for the ELLIPTA® dry powder inhaler over a commonly used single-dose capsule dry powder inhaler by inhalation device-naïve Japanese volunteers aged 40 years or older. Int J COPD. 2014;9:1365–75.

    Article  Google Scholar 

  49. Svedsater H, Dale P, Garrill K, Walker R, Woepse MW. Qualitative assessment of attributes and ease of use of the ELLIPTA™ dry powder inhaler for delivery of maintenance therapy for asthma and COPD. BMC Pulm Med. 2013;13:72.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Spiriva (package insert). Conn. Boehringer Ingelheim Pharmaceuticals. 2015.

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Authors and Affiliations

  1. Duke University Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Asthma, Allergy, and Airways Center, 1821 Hillandale Rd Suite 25A, Durham, NC, 27705, USA

    Roy A. Pleasants

  2. Department of Pharmacy Administration and Clinical Pharmacy, Peking University Health Science Center, Beijing, China

    Tiansheng Wang

  3. Department of Respiratory Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

    Jinming Gao

  4. Department of Pharmacy, Peking University Third Hospital, Beijing, China

    Huilin Tang

  5. Division of Pulmonary Diseases and Critical Care Medicine, UNC Chapel Hill, Chapel Hill, NC, USA

    James F. Donohue

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  1. Roy A. Pleasants
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  2. Tiansheng Wang
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  3. Jinming Gao
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  4. Huilin Tang
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Correspondence to Roy A. Pleasants.

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RP declares research relationships with Astra Zeneca, Boehringer Ingelheim, Genentech, Glaxo Smith Kline, and TEVA. TW and HL have no conflicts of interest to disclose. JG has acted as a consultant to Novartis. JD has served as a consultant and/or on the Data Safety Monitoring Board for Astra Zeneca, Boehringer Ingelheim, Gilead, Glaxo Smith Kline, Novartis, and Sunovion.

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Pleasants, R.A., Wang, T., Gao, J. et al. Inhaled Umeclidinium in COPD Patients: A Review and Meta-Analysis. Drugs 76, 343–361 (2016). https://doi.org/10.1007/s40265-015-0532-5

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