Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT)

Respiratory Research

Esther Garcia Gil⁴  Anne Leselbaum¹  Eduard Molins⁴  Anthony D. D’Urzo⁵  Dave Singh⁶  Kenneth R. Chapman²  Eric D. Bateman³ 

[1] Former employee of Almirall S.A., Barcelona, Spain;Asthma & Airway Centre, University Health Network, Toronto Western Hospital, Toronto, ON, Canada;Division of Pulmonology, Department of Medicine, University of Cape Town, George Street, Mowbray 7700, Cape Town, South Africa;R&D Centre, AstraZeneca PLC (former employee of Almirall S.A.), Barcelona, Spain;Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada;University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester, Manchester, UK

关键词: Symptoms;    Fixed-dose combination;    Chronic obstructive pulmonary disease;    Aclidinium bromide/formoterol fumarate;   

Others  :  1227509
DOI  :  10.1186/s12931-015-0250-2

 received in 2015-01-26, accepted in 2015-07-08,  发布年份 2015

【 摘 要 】

Background

The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta ₂ -agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment. The effect of this combination on symptoms of COPD and exacerbations is less well established. We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).

Methods

Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV ₁ ]/forced vital capacity <70 % and FEV ₁  ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®. Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.

Results

The pooled intent-to-treat population included 3394 patients. Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05). Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05). The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05). Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies. Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).

Conclusions

Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD. Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.

Trial registration

NCT01462942 and NCT01437397 (ClinicalTrials.gov)

【 授权许可】

   
2015 Bateman et al.

【 图 表 】

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