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Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial.

Abstract

OBJECTIVE

The aim of this study was to assess the efficacy and tolerability of nebulized arformoterol tartrate (a selective, long-acting beta(2)-adrenergic agonist that is the [R,R] isomer of formoterol) and salmeterol xinafoate versus placebo in patients with chronic obstructive pulmonary disease (COPD).

METHODS

This 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial was conducted at 60 centers across the United States. Male and female patients aged >or=35 years with physician-diagnosed COPD received arformoterol (15 microg BID, 25 microg BID, or 50 microg QD via nebulizer), salmeterol (42 microg BID via metered dose inhaler), or placebo. Pulmonary function was assessed by spirometry; dyspnea, by the Transitional Dyspnea Index (TDI); and health status, by the St. George's Respiratory Questionnaire (SGRQ). Adverse events (AEs) were assessed by site personnel at all clinic visits (screening, first dose at week 0, and at weeks 3, 6, 9, 12, and follow-up). COPD exacerbations were defined as worsening respiratory status requiring a change in medication or an unscheduled provider visit.

RESULTS

A total of 717 patients received study medication. The demographic composition of all treatment arms was similar. The mean age was 62.9 years, 58% were men, and mean baseline forced expiratory volume in 1 second (FEV(1)) was 1.2 L (41% predicted). Mean improvement in trough FEV(1) over 12 weeks was significantly greater with all 3 arformoterol doses (15 microg BID, +16.9%; 25 microg BID, +18.9%; 50 microg QD, +14.9%) and for salmeterol (+17.4%) relative to placebo (+6.0%; P < 0.001). There were significantly greater improvements in the mean percentage change in FEV(1) AUC(0-12h) from the predose value over 12 weeks (15 microg BID, 12.7%, 25 microg BID, 13.9%, 50 microg QD, 18.9%; salmeterol, 9.8%) versus placebo (2.7%; P <or= 0.001); all doses of arformoterol were statistically different from salmeterol for this end point (P <or= 0.024). At week 12, TDI focal scores were significantly greater with all arformoterol doses compared with placebo (mean [95% CI]: 15 microg BID, 0.97 [0.25-1.69]; 25 microg BID, 1.08 [0.3-1.86]; 50 microg QD, 1.04 [0.32-1.771), suggesting treatment-associated improvement in dyspnea, however, the difference between salmeterol and placebo was not statistically significant (0.36 [-0.40 to 1.12]). Improvements in health status, as measured using SGRQ total scores, were -2.6 to -3.6 U in the arformoterol groups, -4.4 U for salmeterol, and -1.2 U for placebo; 95% CI of differences versus placebo suggested significant improvement for the arformoterol 25 microg BID and salmeterol groups. There was a similar frequency of AEs and COPD exacerbations across all groups, including placebo.

CONCLUSIONS

In this trial, patients with moderate to severe COPD administered nebulized arformoterol over 12 weeks were observed to have significant and sustained improvements in airway function and dyspnea compared with placebo. The results also suggest that all doses of arformoterol, including the lowest dose (15 microg BID), were effective. Overall, nebulized arformoterol was well tolerated.

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  • Authors+Show Affiliations

    ,

    Sepracor Inc., Marlborough, Massachusetts 01752, USA.

    , , , ,

    Source

    Clinical therapeutics 29:2 2007 Feb pg 261-78

    MeSH

    Administration, Inhalation
    Adrenergic beta-Agonists
    Aged
    Albuterol
    Bronchodilator Agents
    Dose-Response Relationship, Drug
    Double-Blind Method
    Dyspnea
    Ethanolamines
    Female
    Forced Expiratory Volume
    Formoterol Fumarate
    Humans
    Male
    Metered Dose Inhalers
    Middle Aged
    Nebulizers and Vaporizers
    Pulmonary Disease, Chronic Obstructive
    Salmeterol Xinafoate
    Severity of Illness Index
    Spirometry
    Treatment Outcome

    Pub Type(s)

    Comparative Study
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17472819

    Citation

    Baumgartner, Rudolf A., et al. "Nebulized Arformoterol in Patients With COPD: a 12-week, Multicenter, Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled Trial." Clinical Therapeutics, vol. 29, no. 2, 2007, pp. 261-78.
    Baumgartner RA, Hanania NA, Calhoun WJ, et al. Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial. Clin Ther. 2007;29(2):261-78.
    Baumgartner, R. A., Hanania, N. A., Calhoun, W. J., Sahn, S. A., Sciarappa, K., & Hanrahan, J. P. (2007). Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial. Clinical Therapeutics, 29(2), pp. 261-78.
    Baumgartner RA, et al. Nebulized Arformoterol in Patients With COPD: a 12-week, Multicenter, Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled Trial. Clin Ther. 2007;29(2):261-78. PubMed PMID: 17472819.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial. AU - Baumgartner,Rudolf A, AU - Hanania,Nicola A, AU - Calhoun,William J, AU - Sahn,Steven A, AU - Sciarappa,Kenneth, AU - Hanrahan,John P, PY - 2007/01/12/accepted PY - 2007/5/3/pubmed PY - 2007/8/8/medline PY - 2007/5/3/entrez SP - 261 EP - 78 JF - Clinical therapeutics JO - Clin Ther VL - 29 IS - 2 N2 - OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of nebulized arformoterol tartrate (a selective, long-acting beta(2)-adrenergic agonist that is the [R,R] isomer of formoterol) and salmeterol xinafoate versus placebo in patients with chronic obstructive pulmonary disease (COPD). METHODS: This 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial was conducted at 60 centers across the United States. Male and female patients aged >or=35 years with physician-diagnosed COPD received arformoterol (15 microg BID, 25 microg BID, or 50 microg QD via nebulizer), salmeterol (42 microg BID via metered dose inhaler), or placebo. Pulmonary function was assessed by spirometry; dyspnea, by the Transitional Dyspnea Index (TDI); and health status, by the St. George's Respiratory Questionnaire (SGRQ). Adverse events (AEs) were assessed by site personnel at all clinic visits (screening, first dose at week 0, and at weeks 3, 6, 9, 12, and follow-up). COPD exacerbations were defined as worsening respiratory status requiring a change in medication or an unscheduled provider visit. RESULTS: A total of 717 patients received study medication. The demographic composition of all treatment arms was similar. The mean age was 62.9 years, 58% were men, and mean baseline forced expiratory volume in 1 second (FEV(1)) was 1.2 L (41% predicted). Mean improvement in trough FEV(1) over 12 weeks was significantly greater with all 3 arformoterol doses (15 microg BID, +16.9%; 25 microg BID, +18.9%; 50 microg QD, +14.9%) and for salmeterol (+17.4%) relative to placebo (+6.0%; P < 0.001). There were significantly greater improvements in the mean percentage change in FEV(1) AUC(0-12h) from the predose value over 12 weeks (15 microg BID, 12.7%, 25 microg BID, 13.9%, 50 microg QD, 18.9%; salmeterol, 9.8%) versus placebo (2.7%; P <or= 0.001); all doses of arformoterol were statistically different from salmeterol for this end point (P <or= 0.024). At week 12, TDI focal scores were significantly greater with all arformoterol doses compared with placebo (mean [95% CI]: 15 microg BID, 0.97 [0.25-1.69]; 25 microg BID, 1.08 [0.3-1.86]; 50 microg QD, 1.04 [0.32-1.771), suggesting treatment-associated improvement in dyspnea, however, the difference between salmeterol and placebo was not statistically significant (0.36 [-0.40 to 1.12]). Improvements in health status, as measured using SGRQ total scores, were -2.6 to -3.6 U in the arformoterol groups, -4.4 U for salmeterol, and -1.2 U for placebo; 95% CI of differences versus placebo suggested significant improvement for the arformoterol 25 microg BID and salmeterol groups. There was a similar frequency of AEs and COPD exacerbations across all groups, including placebo. CONCLUSIONS: In this trial, patients with moderate to severe COPD administered nebulized arformoterol over 12 weeks were observed to have significant and sustained improvements in airway function and dyspnea compared with placebo. The results also suggest that all doses of arformoterol, including the lowest dose (15 microg BID), were effective. Overall, nebulized arformoterol was well tolerated. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/17472819/Nebulized_arformoterol_in_patients_with_COPD:_a_12_week_multicenter_randomized_double_blind_double_dummy_placebo__and_active_controlled_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(07)00050-1 DB - PRIME DP - Unbound Medicine ER -