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Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study

BACKGROUND: Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combinat...

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Autores principales: D’Urzo, Anthony D, Rennard, Stephen I, Kerwin, Edward M, Mergel, Victor, Leselbaum, Anne R, Caracta, Cynthia F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213545/
https://www.ncbi.nlm.nih.gov/pubmed/25756831
http://dx.doi.org/10.1186/s12931-014-0123-0
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author D’Urzo, Anthony D
Rennard, Stephen I
Kerwin, Edward M
Mergel, Victor
Leselbaum, Anne R
Caracta, Cynthia F
author_facet D’Urzo, Anthony D
Rennard, Stephen I
Kerwin, Edward M
Mergel, Victor
Leselbaum, Anne R
Caracta, Cynthia F
author_sort D’Urzo, Anthony D
collection PubMed
description BACKGROUND: Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β(2)-agonist, in patients with moderate to severe COPD are presented. METHODS: In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair(®)/Pressair(®))*. Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV(1) (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV(1) (FDCs versus formoterol). Secondary endpoints were change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24. Safety and tolerability were also assessed. RESULTS: At study end, improvements from baseline in 1-hour postdose FEV(1) were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001). Improvements in trough FEV(1) were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV(1) over formoterol was observed with ACL400/FOR6 FDC. Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively. All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies. CONCLUSIONS: Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo. Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD. TRIAL REGISTRATION: Clinicaltrials.gov NCT01437397. *Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair(®) and Genuair(®) within all other licensed territories. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-42135452014-10-31 Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study D’Urzo, Anthony D Rennard, Stephen I Kerwin, Edward M Mergel, Victor Leselbaum, Anne R Caracta, Cynthia F Respir Res Research BACKGROUND: Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β(2)-agonist, in patients with moderate to severe COPD are presented. METHODS: In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair(®)/Pressair(®))*. Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV(1) (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV(1) (FDCs versus formoterol). Secondary endpoints were change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24. Safety and tolerability were also assessed. RESULTS: At study end, improvements from baseline in 1-hour postdose FEV(1) were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001). Improvements in trough FEV(1) were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV(1) over formoterol was observed with ACL400/FOR6 FDC. Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively. All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies. CONCLUSIONS: Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo. Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD. TRIAL REGISTRATION: Clinicaltrials.gov NCT01437397. *Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair(®) and Genuair(®) within all other licensed territories. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-14 2014 /pmc/articles/PMC4213545/ /pubmed/25756831 http://dx.doi.org/10.1186/s12931-014-0123-0 Text en © D'Urzo et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
D’Urzo, Anthony D
Rennard, Stephen I
Kerwin, Edward M
Mergel, Victor
Leselbaum, Anne R
Caracta, Cynthia F
Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study
title Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study
title_full Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study
title_fullStr Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study
title_full_unstemmed Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study
title_short Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study
title_sort efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled augment copd study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213545/
https://www.ncbi.nlm.nih.gov/pubmed/25756831
http://dx.doi.org/10.1186/s12931-014-0123-0
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