Safety and efficacy of fluticasone propionate/salmeterol hydrofluoroalkane 134a metered-dose-inhaler compared with fluticasone propionate/salmeterol diskus in patients with chronic obstructive pulmonary disease

Andras Koser, Jan Westerman, Sanjay Sharma, Amanda Emmett, Glenn D Crater, Andras Koser, Jan Westerman, Sanjay Sharma, Amanda Emmett, Glenn D Crater

Abstract

Purpose: To provide information on the efficacy and safety of Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a Metered-Dose-Inhaler 230/42mcg (FSC MDI) and its comparable dose of Fluticasone Propionate/Salmeterol DISKUS 250/50mcg (FSC DISKUS) in patients with COPD.

Methods: This multicenter, randomized, double-blind, 12 week study was designed to evaluate FSC MDI treatment responses as compared with FSC DISKUS. The primary comparison of interest was non-inferiority between the FSC MDI treatment group and the FSC DISKUS treatment group assessed in terms of 2-hour post-dose FEV(1) change from baseline at endpoint. The non-inferiority criterion bound was 75mL (lower confidence limit of -75mL).

Inclusion criteria: Male or female aged ≥ 40, post-bronchodilator FEV(1) ≤ 70% predicted normal, FEV(1)/FVC ≤ 70% and ≥ 10 pack years smoking history. Adverse events were recorded by patients throughout the study on daily diary cards. Adverse events were collected in eCRFs at all clinic visits and during a final follow-up phone call.

Results: Patients (N=247) were randomized to FSC MDI (FEV(1)% 49.3 ± 12.3, FEV(1)/FVC 50.5 ± 10.0) and FSC DISKUS (FEV(1)% 48.4 ± 11.0, FEV(1)/FVC 50.3 ± 10.3). From an ANCOVA model the least squares (LS) mean difference (FSC MDI- FSC DISKUS) for the 2-hour post dose FEV(1) at endpoint was -2.0mL (95% CI -64mL, 59mL). Pre-dose FEV(1), FVC, PEF, and albuterol use were also similar between the two formulations. The most common adverse events (AE) during treatment were headache (8% and 6% of patients), nasopharyngitis (4% and 6%), cough (3% and 4%), and sinusitis (2% and 5%) for FSC MDI and FSC DISKUS, respectively. Pneumonia was recorded as an AE for 2 (2%) patients in the FSC DISKUS arm.

Conclusion: This is the first study to demonstrate that FSC MDI has a similar efficacy and safety profile to FSC DISKUS in COPD patients.

Keywords: Chronic Obstructive Pulmonary Disease (COPD); Fluticasone Propionate/Salmeterol (FSC) DISKUS; HFA; Inhaled Corticosteroid..

Figures

Fig. (1)
Fig. (1)
Enrollment of patients and reasons for withdrawal.
Fig. (2)
Fig. (2)
Mean change from baseline in 2-Hour post-dose FEV1 (primary endpoint).

References

    1. 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;23:932–46.
    1. 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;19:217–24.
    1. Hanania NA, Darken P, Horstman D, et al. The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD. Chest. 2003;124:834–43.
    1. Rennard SI, Anderson W, ZuWallack R, et al. Use of a long-acting inhaled beta 2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;163:1087–92.
    1. O'Donnell DE, Sciurba F, Celli B, et al. Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD. Chest. 2006;130:647–56.
    1. Anzueto A, Ferguson GT, Feldman G, et al. Effect of fluticasone propionate/salmeterol (250/50) on COPD exacerbations and impact on patient outcomes. J COPD. 2009;6:320–29.
    1. Calverley PMA, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775–89.
    1. Ferguson GT, Anzueto A, Fei R, et al. Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations. Respir Med. 2008;102:1099–108.
    1. Nathan RA, Rooklin A, Schoaf L, et al. Efficacy and tolerability of fluticasone propionate/salmeterol administered twice daily via hydrofluoroalkane 134a metered-dose inhaler in adolescent and adult patients with persistent asthma: A randomized, double-blind, placebo-controlled, 12-week study. Clin Therap. 2006;28:73–85.
    1. Nelson HS, Wolfe JD, Gross G, et al. Efficacy and safety of fluticasone propionate 44 µg/salmeterol 21 µg administered in a hydrofluoroalkane metered-dose inhaler as an initial asthma maintenance treatment. Ann Allergy Asthma Immunol. 2003;91:263–9.
    1. Pearlman DS, Peden D, Condemi JJ, et al. Efficacy and safety of fluticasone propionate/salmeterol HFA 134A MDI in patients with mild-to-moderate persistent asthma. J Asthma. 2004;41:797–806.
    1. Dolovich MB, Ahrens RC, Hess DR, et al. Device selection and outcomes of aerosol therapy: Evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005;127:335–71.
    1. Khassawneh BY, Al Ali MK, Alzoubi KH, et al. Handling of inhaler devices in actual pulmonary practice: Metered-dose inhaler versus dry powder inhalers. Respir Care. 2008;53:324–28.
    1. Schulte M, Osseiran K, Betz R, et al. Handling of and preferences for available dry powder inhaler systems by patients with asthma and COPD. J Aerosol Med Pulm Drug Deliv. 2008;21:321–28.
    1. Sheth K, Bernstein JA, Lincourt WR, et al. Patient perceptions of an inhaled asthma medication administered as an inhalation powder via the Diskus or as an inhalation aerosol via a metered-dose inhaler. Ann Allergy Asthma Immunol. 2003;91:55–60.

Source: PubMed

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