University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester, Langley Building, Southmoor Road, Manchester M23 9QZ, UK.
Pulm Pharmacol Ther. 2012 Jun;25(3):248-53. doi: 10.1016/j.pupt.2012.03.008. Epub 2012 Apr 4.
This Phase IIb, double-blind, double-dummy, placebo- and active-comparator-controlled crossover study (ClinicalTrials.gov identifier: NCT01120093) assessed efficacy and safety of three doses of aclidinium bromide in patients with moderate to severe chronic obstructive pulmonary disease. Patients were randomised to one of five treatment sequences each consisting of twice-daily (BID) aclidinium 100 μg, 200 μg, 400 μg (via Genuair®*), formoterol 12 μg (via Aerolizer®) and matched placebo for 7 days, with a 5- to 9-day washout period. Primary endpoint was mean change from baseline in forced expiratory volume in 1 s (FEV1) normalised area under the curve (AUC)0-12 on Day 7. Secondary endpoints were: change from baseline in FEV1 normalised AUC12-24, FEV1 normalised AUC0-24 and morning pre-dose FEV1 on Day 7. Adverse events were monitored throughout the study. Of 79 randomised patients, 68 (86.1%) completed the study. After 7 days of treatment, aclidinium and formoterol produced statistically significantly greater changes from baseline in FEV1 normalised AUC0-12 vs placebo (p<0.0001). FEV1 normalised AUC12-24, FEV1 normalised AUC0-24, and morning pre-dose FEV1 were also statistically significantly greater with all aclidinium doses vs placebo (p<0.0001). Improvements in primary and secondary endpoints were statistically significantly greater with aclidinium 400 μg vs 100 μg. The safety profile of aclidinium was comparable to placebo. These results demonstrated that twice-daily aclidinium produced dose-dependent clinically meaningful improvements in FEV1 compared with placebo. This study also confirmed the use of an aclidinium BID dosing regimen and established aclidinium 200 μg and 400 μg as suitable doses for further investigation in Phase III trials.
这项 IIb 期、双盲、双模拟、安慰剂和阳性对照交叉研究（ClinicalTrials.gov 标识符：NCT01120093）评估了三种剂量的阿地溴铵在中重度慢性阻塞性肺疾病患者中的疗效和安全性。患者随机分为五组治疗序列中的一组，每组均接受每日两次（BID）阿地溴铵 100μg、200μg、400μg（通过 Genuair®*）、福莫特罗 12μg（通过 Aerolizer®）和匹配的安慰剂治疗 7 天，然后进行 5-9 天的洗脱期。主要终点是第 7 天用力呼气量（FEV1）与正常化面积曲线下面积（AUC）0-12 的平均变化。次要终点是：第 7 天 FEV1 与正常化 AUC12-24、FEV1 与正常化 AUC0-24 和清晨预剂量 FEV1 的变化。在整个研究过程中监测不良事件。在 79 名随机患者中，68 名（86.1%）完成了研究。经过 7 天的治疗，阿地溴铵和福莫特罗与安慰剂相比，FEV1 与正常化 AUC0-12 的变化具有统计学意义（p<0.0001）。所有阿地溴铵剂量与安慰剂相比，FEV1 与正常化 AUC12-24、FEV1 与正常化 AUC0-24 和清晨预剂量 FEV1 也具有统计学意义（p<0.0001）。与 100μg 相比，阿地溴铵 400μg 剂量的主要和次要终点改善具有统计学意义。阿地溴铵的安全性与安慰剂相当。这些结果表明，与安慰剂相比，每日两次阿地溴铵可使 FEV1 产生剂量依赖性的临床有意义的改善。该研究还证实了阿地溴铵每日两次给药方案的应用，并确定了阿地溴铵 200μg 和 400μg 是进一步进行 III 期试验的合适剂量。
