Bronchodilator efficacy of 18 μg once-daily tiotropium inhalation via Discair® versus HandiHaler® in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial

Pinar Yildiz, Mesut Bayraktaroglu, Didem Gorgun, Funda Secik, Pinar Yildiz, Mesut Bayraktaroglu, Didem Gorgun, Funda Secik

Abstract

Purpose: To compare the bronchodilator efficacy of 18 μg once-daily tiotropium inhalation administered via Discair® versus HandiHaler® in adults with moderate-to-severe chronic obstructive pulmonary disease (COPD).

Patients and methods: Fifty-eight patients with moderate-to-severe COPD were enrolled in this randomized, active-controlled, parallel-group, open-label, Phase IV non-inferiority trial. Patients were randomly assigned to a test group (n=29, inhalation with Discair) or a reference group (n=29, inhalation with HandiHaler). The primary efficacy parameter was the average maximum change in forced expiratory volume in 1 second (FEV1, in L). Change in forced vital capacity (FVC, in L), %FEV1 and %FVC, the standardized area under the response-time curve (AUC) for the absolute change in FEV1 and FVC, time to onset and peak of response, and safety data were also evaluated.

Results: The test inhaler was non-inferior to the reference inhaler in terms of maximum change in FEV1 at 24 h (unadjusted change: 0.0017 L [95% confidence interval [CI]: -0.0777, 0.0812]; change adjusted for time to reach maximum change in FEV1 and smoking in pack-years: 0.0116 L [95% CI: -0.0699, 0.0931]), based on a non-inferiority margin of 0.100 L. There were also no significant differences between the two groups in maximum change in FVC value from baseline (0.3417 L vs 0.4438 L, P=0.113), percent change from baseline (22.235 vs 20.783 for FEV1, P=0.662; 16.719 vs 20.337 for FVC, P=0.257), and AUC0-24 h (2.949 vs 2.833 L for FEV1, P=0.891; 2.897 vs 4.729 L for FVC, P=0.178). There were no adverse events, serious adverse events, or deaths.

Conclusion: Our findings show that the Discair was non-inferior to the HandiHaler. More specifically, these devices had similar clinical efficacy in terms of time-dependent response over 24 h for patients with moderate-to-severe COPD.

Keywords: Discair®; HandiHaler®; bronchodilator efficacy; non-inferiority; spirometry; tiotropium.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Maximum change in forced expiratory volume in 1 second (FEV1, top) and forced vital capacity (FVC, bottom) from baseline (pretreatment, 0 h) to 24 h after bronchodilator treatment in the reference group (HandiHaler®) and the test group (Discair®).

References

    1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016. [Accessed May 1, 2016]. Available from:
    1. Qaseem A, Wilt TJ, Weinberger SE, et al. American College of Physicians. American College of Chest Physicians. American Thoracic Society; European Respiratory Society Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011;155(3):179–191.
    1. Janson C, Marks G, Buist S, et al. The impact of COPD on health status: findings from the BOLD study. Eur Respir J. 2013;42(6):1472–1483.
    1. Lopez-Campos JL, Hartl S, Pozo-Rodriguez F, Roberts CM, European COPD Audit team Variability of hospital resources for acute care of COPD patients: the European COPD audit. Eur Respir J. 2014;43(3):754–762.
    1. World Health Organization . COPD predicted to be third leading cause of death in 2030 [webpage on the Internet] Geneva: World Health Organization; 2008. [Accessed December 25, 2015]. Available from: .
    1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2007;3(11):e442.
    1. Yohannes AM, Connolly MJ, Hanania NA. Ten years of tiotropium: clinical impact and patient perspectives. Int J Chron Obstruct Pulmon Dis. 2013;8:117–125.
    1. Alvarado-Gonzalez A, Arce I. Tiotropium bromide in chronic obstructive pulmonary disease and bronchial asthma. J Clin Med Res. 2015;7(11):831–839.
    1. Tashkin DP, Celli B, Senn S, et al. for UPLIFT study investigators A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543–1554.
    1. Halpin DM, Dahl R, Hallmann C, Mueller A, Tashkin D. Tiotropium HandiHaler® and Respimat® in COPD: a pooled safety analysis. Int J Chron Obstruct Pulmon Dis. 2015;10:239–259.
    1. Verhamme KM, Afonso A, Romio S, Stricker BC, Brusselle GG, Sturkenboom MC. Use of tiotropium respimat soft mist Inhaler versus HandiHaler and mortality in patients with COPD. Eur Respir J. 2013;42(3):606–615.
    1. Bourbeau J, Bartlett SJ. Patient adherence in COPD. Thorax. 2008;63(9):831–838.
    1. Halpern R, Baker CL, Su J, et al. Outcomes associated with initiation of tiotropium or fluticasone/salmeterol in patients with chronic obstructive pulmonary disease. Patient Prefer Adherence. 2011;5:375–388.
    1. Koehorst-ter Huurne K, Movig K, van der Valk P, van der Palen J, Brusse-Keizer M. Differences in adherence to common inhaled medications in COPD. COPD. 2015;12(6):643–648.
    1. Boehringer Ingelheim Spiriva 18 microgram inhalation powder, hard capsule. Summary of Product Characteristics (SPC), Electronic Medicines Compendium (EMC) [Accessed December 19, 2015]. Available from:
    1. Boehringer Ingelheim Spiriva Respimat 2.5 microgram solution for inhalation. Summary of Product Characteristics (SPC), Electronic Medicines Compendium (EMC) [Accessed December 19, 2015]. Available from: .
    1. Boehringer Ingelheim . Boehringer Ingelheim submits application in Europe to extend the indication for the use of tiotropium Respimat® to the treatment of asthma in adults aged 18 years and over [press release archive: asthma] Ingelheim, Germany: Boehringer Ingelheim; 2013. Nov 13, [Accessed December 19, 2015]. Available from: .
    1. George J, Kong DCM, Thoman R, Stewart K. Factors associated with medication non-adherence in patients with COPD. Chest. 2005;128(5):3198–3204.
    1. Hanada S, Wada S, Ohno T, Sawaguchi H, Muraki M, Tohda Y. Questionnaire on switching from the tiotropium HandiHaler to the Respimat inhaler in patients with chronic obstructive pulmonary disease: changes in handling and preferences immediately and several years after the switch. Int J Chron Obstruct Pulmon Dis. 2015;10:69–77.
    1. Rand CS. Patient adherence with COPD therapy. Eur Respir Rev. 2005;14:97–101.
    1. Cazzola M, Matera MG. Novel long-acting bronchodilators for COPD and asthma. Br J Pharmacol. 2008;155(3):291–299.
    1. Bateman ED. Improving inhaler use in COPD and the role of patient preference. Eur Respir Rev. 2005;14:85–88.
    1. Chapman KR, Fogarty CM, Peckitt C, et al. Delivery characteristics and patients’ handling of two single-dose dry-powder inhalers used in COPD. Int J Chron Obstruct Pulmon Dis. 2011;6:353–363.
    1. Hesselink AE, Penninx BW, Wijnhoven HA, Kriegsman DM, van Eijk JT. Determinants of an incorrect inhalation technique in patients with asthma or COPD. Scand J Prim Health Care. 2001;19(4):255–260.
    1. Vincken W, Dekhuijzen PR, Barnes P, ADMIT Group The ADMIT series – Issues in inhalation therapy. 4) How to choose inhaler devices for the treatment of COPD. Prim Care Respir J. 2010;19(1):10–20.
    1. Fromer L, Goodwin E, Walsh J. Customizing inhaled therapy to meet the needs of COPD patients. Postgrad Med. 2010;122(2):83–93.
    1. Mäkelä MJ, Backer V, Hedegaard M, Larsson K. Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD. Respir Med. 2013;107(10):1481–1490.
    1. Gupta S. How to ensure the correct inhaler device is selected for each patient. Clin Pharmacist. 2009;1:322–323.
    1. Dahl R, Backer V, Ollgaard B, Gerken F, Kesten S. Assessment of patient performance of the HandiHaler compared with the metered dose inhaler four weeks after instruction. Respir Med. 2003;97(10):1126–1133.
    1. Ruchi T, Vishal S, Neetu K, Vikramjeet S. Recent trends in DPI technology. Int Res J Pharm. 2012;3(1):27–34.
    1. Nicolai JL, Torvinen S, Miles R, Greaney MH, Howard DJ, Plich A. The potential societal cost benefits of increasing patient satisfaction by using an inhaler with improved features compared to Spiriva® HandiHaler® for the management of chronic obstructive pulmonary disease (COPD) in the UK. Value Health. 2015;18:A500.
    1. Van Der Palen J, Eijsvogel MM, Kuipers BF, Schipper M, Vermue NA. Comparison of the Diskus inhaler and the HandiHaler regarding preference and ease of use. J Aerosol Med. 2007;20(1):38–44.
    1. Chorão P, Pereira AM, Fonseca JA. Inhaler devices in asthma and COPD-an assessment of inhaler technique and patient preferences. Respir Med. 2014;108(7):968–975.
    1. Hanania NA, Sharma G, Sharafkhaneh A. COPD in the elderly patient. Semin Respir Crit Care Med. 2010;31(5):596–606.
    1. Taffet GE, Donohue JF, Altman PR. Considerations for managing chronic obstructive pulmonary disease in the elderly. Clin Interv Aging. 2014;9:23–30.
    1. Hodder R, Price D. Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat Soft Mist inhaler. Int J Chron Obstruct Pulmon Dis. 2009;4:381–390.
    1. Neutec Tiofix Discair Product information. [Accessed January 14, 2016]. Available from: .
    1. Lopez-Campos JL, Calero C, Lopez-Ramirez C, Asensio-Cruz MI, Márquez-Martín E, Ortega-Ruiz F. Patient-reported outcomes and considerations in the management of COPD: focus on aclidinium. Patient Prefer Adher. 2015;9:95–104.
    1. Brashier B, Dhembare P, Jantikar A, et al. Tiotropium administered by a pressurized metered dose inhaler (pMDI) and spacer produces a similar bronchodilator response as that administered by a Rotahaler in adult subjects with stable moderate-to-severe COPD. Respir Med. 2007;101(12):2464–2471.
    1. Shavro SA, Ezhilarasu P, Augustine J, Bechtel JJ, Christopher DJ. Correlation of health-related quality of life with other disease severity indices in Indian chronic obstructive pulmonary disease patients. Int J Chron Obstruct Pulmon Dis. 2012;7:291–296.
    1. 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.
    1. Lopez-Campos JL, Bustamante V, Munoz X, Barreiro E. Moving towards patient-centered medicine for COPD management: multidimensional approaches versus phenotype-based medicine – a critical view. Chronic Obstr Pulm Dis. 2014;11(5):591–602.
    1. Vestbo J, Hurd SS, Agustí AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347–365.
    1. Fletcher CM. The clinical diagnosis of pulmonary emphysema; an experimental study. Proc R Soc Med. 1952;45(9):577–584.
    1. Sarinas PS, Robinson TE, Clark AR, Canfield J, Jr, Chitkara RK, Fick RB., Jr Inspiratory flow rate and dynamic lung function in cystic fibrosis and chronic obstructive lung diseases. Chest. 1998;114(4):988–992.
    1. Celli B, ZuWallack R, Wang S, Kesten S. Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes. Chest. 2003;124(5):1743–1748.
    1. O’Donnell DE, Fluge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnea and exercise tolerance in COPD. Eur Respir J. 2004;23(6):832–840.
    1. Celli Bartolome R. Chronic obstructive pulmonary disease phenotypes and their clinical relevance. Proc Am Thorac Soc. 2006;3(6):461–465.
    1. Valente S, Pasciuto G, Bernabei R, Corbo GM. Do we need different treatments for very elderly COPD patients? Respiration. 2010;80(5):357–368.
    1. Decramer M, Molenberghs G, Liu D, et al. UPLIFT investigators Premature discontinuation during the UPLIFT study. Respir Med. 2011;105(10):1523–1530.
    1. Chrystyn H, Small M, Milligan G, Higgins V, Gil EG, Estruch J. Impact of patients’ satisfaction with their inhalers on treatment compliance and health status in COPD. Respir Med. 2014;108(2):358–365.
    1. Ichinose M, Fujimoto T, Fukuchi Y. Tiotropium 5 microg via Respimat and 18 microg via HandiHaler; efficacy and safety in Japanese COPD patients. Respir Med. 2010;104(2):228–236.
    1. Keating GM. Tiotropium bromide inhalation powder: a review of its use in the management of chronic obstructive pulmonary disease. Drugs. 2012;72(2):273–300.
    1. Hohlfeld JM, Sharma A, van Noord JA, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54(4):405–414.

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