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Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study.

Singh D, Jones PW, Bateman ED, Korn S, Serra C, Molins E, Caracta C, Gil EG, Leselbaum A - BMC Pulm Med (2014)

Bottom Line: Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.

View Article: PubMed Central - PubMed

Affiliation: University of Manchester, Medicines Evaluation Unit, Langley Building, University Hospital of South Manchester NHS Foundation Trust, Southmoor Road, Manchester M23 9QZ, UK. dsingh@meu.org.uk.

ABSTRACT

Background: Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD). The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.

Methods: In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.

Results: At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints). Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint). All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.

Conclusions: Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk. Aclidinium/formoterol may be an effective treatment for patients with COPD.

Trial registration: ClinicalTrials.gov: NCT01462942.

No MeSH data available.


Related in: MedlinePlus

Improvement in TDI focal score at 24 weeks (ITT population). Data are presented as least squares means (SE). ***p < 0.001 vs placebo. FDC, aclidinium/formoterol fixed-dose combination; ITT, intent-to-treat; MCID, minimum clinically important difference; SE, standard error; TDI, transition dyspnoea index.
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Fig4: Improvement in TDI focal score at 24 weeks (ITT population). Data are presented as least squares means (SE). ***p < 0.001 vs placebo. FDC, aclidinium/formoterol fixed-dose combination; ITT, intent-to-treat; MCID, minimum clinically important difference; SE, standard error; TDI, transition dyspnoea index.

Mentions: At Week 24, both FDC doses caused clinically significant improvements (≥1 unit) in TDI focal score versus placebo (400/12 μg: 1.29 units and 400/6 μg: 1.16 units; both p < 0.001; Figure 4). Aclidinium and formoterol monotherapies caused significant improvements (both p < 0.005) versus placebo at Week 24 that fell just below the 1-unit threshold. The differences between both FDC doses versus the monotherapies were not statistically significant (Additional file 1: Table S2). A significantly higher proportion of FDC-treated and monotherapy-treated patients had ≥1 unit improvement in TDI focal score at Week 24 versus placebo (Additional file 1: Table S2).Figure 4


Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study.

Singh D, Jones PW, Bateman ED, Korn S, Serra C, Molins E, Caracta C, Gil EG, Leselbaum A - BMC Pulm Med (2014)

Improvement in TDI focal score at 24 weeks (ITT population). Data are presented as least squares means (SE). ***p < 0.001 vs placebo. FDC, aclidinium/formoterol fixed-dose combination; ITT, intent-to-treat; MCID, minimum clinically important difference; SE, standard error; TDI, transition dyspnoea index.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4273456&req=5

Fig4: Improvement in TDI focal score at 24 weeks (ITT population). Data are presented as least squares means (SE). ***p < 0.001 vs placebo. FDC, aclidinium/formoterol fixed-dose combination; ITT, intent-to-treat; MCID, minimum clinically important difference; SE, standard error; TDI, transition dyspnoea index.
Mentions: At Week 24, both FDC doses caused clinically significant improvements (≥1 unit) in TDI focal score versus placebo (400/12 μg: 1.29 units and 400/6 μg: 1.16 units; both p < 0.001; Figure 4). Aclidinium and formoterol monotherapies caused significant improvements (both p < 0.005) versus placebo at Week 24 that fell just below the 1-unit threshold. The differences between both FDC doses versus the monotherapies were not statistically significant (Additional file 1: Table S2). A significantly higher proportion of FDC-treated and monotherapy-treated patients had ≥1 unit improvement in TDI focal score at Week 24 versus placebo (Additional file 1: Table S2).Figure 4

Bottom Line: Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.

View Article: PubMed Central - PubMed

Affiliation: University of Manchester, Medicines Evaluation Unit, Langley Building, University Hospital of South Manchester NHS Foundation Trust, Southmoor Road, Manchester M23 9QZ, UK. dsingh@meu.org.uk.

ABSTRACT

Background: Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD). The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.

Methods: In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.

Results: At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints). Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint). All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.

Conclusions: Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk. Aclidinium/formoterol may be an effective treatment for patients with COPD.

Trial registration: ClinicalTrials.gov: NCT01462942.

No MeSH data available.


Related in: MedlinePlus