在 COPD 患者中，比较与单一成分和安慰剂的疗效和安全性，溴化阿地铵/富马酸福莫特罗固定剂量复方制剂（ACLIFORM-COPD）：一项多中心、随机研究。

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.

机构信息

University of Manchester, Medicines Evaluation Unit, Langley Building, University Hospital of South Manchester NHS Foundation Trust, Southmoor Road, Manchester M23 9QZ, UK.

出版信息

BMC Pulm Med. 2014 Nov 18;14:178. doi: 10.1186/1471-2466-14-178.

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.

背景

阿地溴铵/福莫特罗是一种每日两次（BID）固定剂量复方制剂（FDC），目前正在开发用于慢性阻塞性肺疾病（COPD）。本研究评估了阿地溴铵/福莫特罗在 COPD 患者中的疗效和安全性，与单药治疗和安慰剂进行了比较。

方法

在这项为期 24 周、双盲、平行分组、阳性药物和安慰剂对照、多中心的 III 期研究中，患者（≥40 岁，支气管扩张剂后 1 秒用力呼气容积（FEV1）/用力肺活量 <70%，且 FEV1≥30%但 <80%预计正常）随机按 2:2:2:2:1 比例接受阿地溴铵/福莫特罗 400/12 μg（n=385）或 400/6 μg（n=381）、阿地溴铵 400 μg（n=385）、福莫特罗 12 μg（n=384）或安慰剂（n=194）BID，通过 Genuair®/Pressair®给药。

结果

在第 24 周，阿地溴铵/福莫特罗 400/12 μg 和 400/6 μg 与阿地溴铵相比，1 小时后剂量的 FEV1 显著改善（分别为 125 mL[95%CI：90，160；p<0.001]和 69 mL[95%CI：34，105；p<0.001]）和谷值 FEV1 与福莫特罗相比（分别为 85 mL[95%CI：51，119；p<0.001]和 53 mL[95%CI：19，87；p<0.01]），这是主要疗效终点。此外，阿地溴铵/福莫特罗 400/12 μg 和 400/6 μg 与安慰剂相比，在过渡性呼吸困难指数（TDI）焦点评分方面也显著改善（分别为 1.29 单位[95%CI：0.73，1.86；p<0.001]和 1.16 单位[95%CI：0.59，1.73；p<0.001]），这是次要疗效终点。所有治疗均耐受良好，FDC 的安全性与安慰剂和单药治疗相似。