A randomised double-blind, placebo-controlled, long-term extension study of the efficacy, safety and tolerability of fixed-dose combinations of aclidinium/formoterol or monotherapy in the treatment of chronic obstructive pulmonary disease

Anthony D'Urzo, Stephen Rennard, Edward Kerwin, James F. Donohue, Alejhandra Lei, Eduard Molins, Anne Leselbaum

Research output: Contribution to journalArticle

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Abstract

Introduction Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies (AUGMENT and ACLIFORM) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This Phase III, double-blind, placebo-controlled, 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg (NCT01572792). Methods Patients were randomised in AUGMENT (1:1:1:1:1) to twice-daily AB/FF 400/12 μg, AB/FF 400/6 μg, AB 400 μg, FF 12 μg or placebo. Patients completing AUGMENT were invited to continue the same treatment in the extension. Adverse events (AEs), major adverse cardiovascular events (MACE), laboratory tests, electrocardiograms and vital signs were recorded. Efficacy was assessed. Results Of 1322 patients completing AUGMENT, 921 enrolled and 780 completed the extension. AE incidence was low and comparable across treatment groups; most common were nasopharyngitis (range 4.8%–9.3%), urinary tract infection (range 4.1%–8.8%) and upper respiratory tract infection (range 2.7%–5.5%). Serious AEs (SAEs) and MACE were low (ranges 6.8%–7.7% and 0.5%–1.5%, respectively). Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo. Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies. AB/FF combinations increased the time to first exacerbation by approximately 30% versus placebo (p < 0.05). Conclusion AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs, SAEs and MACE that were comparable across treatment groups. Improvements in bronchodilation, symptoms and health status were maintained across 52 weeks.

LanguageEnglish (US)
Pages39-48
Number of pages10
JournalRespiratory Medicine
Volume125
DOIs
StatePublished - Apr 1 2017

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Chronic Obstructive Pulmonary Disease
Placebos
Safety
Health Status
Nasopharyngitis
Therapeutics
Vital Signs
Incidence
Urinary Tract Infections
Respiratory Tract Infections
Dyspnea
Formoterol Fumarate
aclidinium bromide
Electrocardiography

Keywords

  • Aclidinium
  • Clinical trial
  • Combination therapy
  • COPD
  • Formoterol

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

A randomised double-blind, placebo-controlled, long-term extension study of the efficacy, safety and tolerability of fixed-dose combinations of aclidinium/formoterol or monotherapy in the treatment of chronic obstructive pulmonary disease. / D'Urzo, Anthony; Rennard, Stephen; Kerwin, Edward; Donohue, James F.; Lei, Alejhandra; Molins, Eduard; Leselbaum, Anne.

In: Respiratory Medicine, Vol. 125, 01.04.2017, p. 39-48.

Research output: Contribution to journalArticle

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abstract = "Introduction Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies (AUGMENT and ACLIFORM) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This Phase III, double-blind, placebo-controlled, 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg (NCT01572792). Methods Patients were randomised in AUGMENT (1:1:1:1:1) to twice-daily AB/FF 400/12 μg, AB/FF 400/6 μg, AB 400 μg, FF 12 μg or placebo. Patients completing AUGMENT were invited to continue the same treatment in the extension. Adverse events (AEs), major adverse cardiovascular events (MACE), laboratory tests, electrocardiograms and vital signs were recorded. Efficacy was assessed. Results Of 1322 patients completing AUGMENT, 921 enrolled and 780 completed the extension. AE incidence was low and comparable across treatment groups; most common were nasopharyngitis (range 4.8\{%}–9.3\{%}), urinary tract infection (range 4.1\{%}–8.8\{%}) and upper respiratory tract infection (range 2.7\{%}–5.5\{%}). Serious AEs (SAEs) and MACE were low (ranges 6.8\{%}–7.7\{%} and 0.5\{%}–1.5\{%}, respectively). Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo. Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies. AB/FF combinations increased the time to first exacerbation by approximately 30\{%} versus placebo (p < 0.05). Conclusion AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs, SAEs and MACE that were comparable across treatment groups. Improvements in bronchodilation, symptoms and health status were maintained across 52 weeks.",
keywords = "Aclidinium, Clinical trial, Combination therapy, COPD, Formoterol",
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T1 - A randomised double-blind, placebo-controlled, long-term extension study of the efficacy, safety and tolerability of fixed-dose combinations of aclidinium/formoterol or monotherapy in the treatment of chronic obstructive pulmonary disease

AU - D'Urzo,Anthony

AU - Rennard,Stephen

AU - Kerwin,Edward

AU - Donohue,James F.

AU - Lei,Alejhandra

AU - Molins,Eduard

AU - Leselbaum,Anne

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Introduction Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies (AUGMENT and ACLIFORM) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This Phase III, double-blind, placebo-controlled, 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg (NCT01572792). Methods Patients were randomised in AUGMENT (1:1:1:1:1) to twice-daily AB/FF 400/12 μg, AB/FF 400/6 μg, AB 400 μg, FF 12 μg or placebo. Patients completing AUGMENT were invited to continue the same treatment in the extension. Adverse events (AEs), major adverse cardiovascular events (MACE), laboratory tests, electrocardiograms and vital signs were recorded. Efficacy was assessed. Results Of 1322 patients completing AUGMENT, 921 enrolled and 780 completed the extension. AE incidence was low and comparable across treatment groups; most common were nasopharyngitis (range 4.8%–9.3%), urinary tract infection (range 4.1%–8.8%) and upper respiratory tract infection (range 2.7%–5.5%). Serious AEs (SAEs) and MACE were low (ranges 6.8%–7.7% and 0.5%–1.5%, respectively). Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo. Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies. AB/FF combinations increased the time to first exacerbation by approximately 30% versus placebo (p < 0.05). Conclusion AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs, SAEs and MACE that were comparable across treatment groups. Improvements in bronchodilation, symptoms and health status were maintained across 52 weeks.

AB - Introduction Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 μg efficacy and safety was demonstrated in two 6-month Phase III studies (AUGMENT and ACLIFORM) and a 12-month study in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This Phase III, double-blind, placebo-controlled, 6-month AUGMENT extension investigated the long-term safety and tolerability of AB/FF 400/12 μg (NCT01572792). Methods Patients were randomised in AUGMENT (1:1:1:1:1) to twice-daily AB/FF 400/12 μg, AB/FF 400/6 μg, AB 400 μg, FF 12 μg or placebo. Patients completing AUGMENT were invited to continue the same treatment in the extension. Adverse events (AEs), major adverse cardiovascular events (MACE), laboratory tests, electrocardiograms and vital signs were recorded. Efficacy was assessed. Results Of 1322 patients completing AUGMENT, 921 enrolled and 780 completed the extension. AE incidence was low and comparable across treatment groups; most common were nasopharyngitis (range 4.8%–9.3%), urinary tract infection (range 4.1%–8.8%) and upper respiratory tract infection (range 2.7%–5.5%). Serious AEs (SAEs) and MACE were low (ranges 6.8%–7.7% and 0.5%–1.5%, respectively). Significant improvements in bronchodilation and dyspnoea were maintained over 52 weeks versus placebo. Trends towards improvements in other symptoms and health status were observed versus placebo and monotherapies. AB/FF combinations increased the time to first exacerbation by approximately 30% versus placebo (p < 0.05). Conclusion AB/FF 400/12 μg was well tolerated over 52 weeks with low incidences of AEs, SAEs and MACE that were comparable across treatment groups. Improvements in bronchodilation, symptoms and health status were maintained across 52 weeks.

KW - Aclidinium

KW - Clinical trial

KW - Combination therapy

KW - COPD

KW - Formoterol

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T2 - Respiratory Medicine

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