University of Manchester, Medicines Evaluation Unit, Langley Building, University Hospital of South Manchester NHS Foundation Trust, Southmoor Road, Manchester M23 9QZ, UK.
BMC Pulm Med. 2014 Nov 18;14:178. doi: 10.1186/1471-2466-14-178.
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.
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.
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.
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.
ClinicalTrials.gov: NCT01462942.
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。
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。
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。
阿地溴铵/福莫特罗 BID 两种剂量均显著改善了与单药治疗相比的支气管扩张作用，与安慰剂相比呼吸困难也得到改善，且安全性风险没有增加。阿地溴铵/福莫特罗可能是治疗 COPD 患者的有效药物。
ClinicalTrials.gov：NCT01462942。
