PAREXEL International GmbH, Berlin, Germany.
Pulmonary Research Institute at Hospital Grosshansdorf, Grosshansdorf, Germany.
Chest. 2012 Mar;141(3):745-752. doi: 10.1378/chest.11-0406. Epub 2011 Sep 8.
The efficacy and safety of aclidinium bromide bid, a novel, long-acting, muscarinic antagonist, was assessed in patients with moderate to severe COPD.
In this phase IIa randomized, double-blind, double-dummy, crossover trial, patients with moderate to severe COPD received aclidinium 400 μg bid, tiotropium 8 μg once daily, and placebo for 15 days, with a 9- to 15-day washout between treatment periods. Treatments were administered through the Genuair or HandiHaler dry powder inhalers. The primary end point was mean change from baseline in FEV(1) AUC(0-12/12h) (area under the curve where the numbers represent the time period for which data were collected divided by the number of hours over which the data are averaged [eg, 0-12 h postdose divided by 12 h]) on day 15. Secondary end points were changes from baseline in FEV(1) AUC(12-24/12h), FEV(1) AUC(0-24/24h), morning predose FEV(1), peak FEV(1), and COPD symptom scores.
Thirty patients with COPD were randomized, and 27 completed the study. Mean change from baseline in FEV(1) AUC(0-12/12h) at day 15 was significantly greater for aclidinium and tiotropium over placebo (P < .0001). Mean changes from baseline in FEV(1) AUC(12-24/12h), FEV(1) AUC(0-24/24h), morning predose FEV(1), and peak FEV(1) at day 15 were significantly greater for aclidinium and tiotropium over placebo (P < .0001 for all except P < .001 for FEV(1) AUC(12-24/12h) tiotropium vs placebo). Improvements were significantly greater with aclidinium vs tiotropium on day 1 for all of the normalized AUC values of FEV(1) as well as on day 15 for FEV(1) AUC(12-24/12h) (P < .05 for all). COPD symptoms were significantly improved from baseline with aclidinium vs placebo (P < .05) but not with tiotropium.
In patients with COPD, aclidinium 400 μg bid compared with placebo provided clinically meaningful improvements in 24-h bronchodilation that generally were comparable to tiotropium 18 μg daily but with significant differences in favor of aclidinium observed in the average nighttime period. Larger studies with longer treatment duration are ongoing to confirm the efficacy of aclidinium 400 μg bid on bronchodilation and COPD symptoms.
ClinicalTrials.gov; No.: NCT00868231; URL: www.clinicaltrials.gov.
新型长效毒蕈碱拮抗剂阿地溴铵 bid 的疗效和安全性在中重度 COPD 患者中进行了评估。
在这项 IIa 期随机、双盲、双模拟、交叉试验中，中重度 COPD 患者接受阿地溴铵 400μg bid、噻托溴铵 8μg 每日一次和安慰剂治疗 15 天，每个治疗期之间有 9-15 天的洗脱期。治疗通过 Genuair 或 HandiHaler 干粉吸入器给药。主要终点是第 15 天 FEV1 AUC（0-12/12h）（曲线下面积，其中数字表示数据采集的时间段除以数据平均的小时数[例如，0-12 小时 postdose 除以 12 小时]）从基线的平均变化。次要终点是 FEV1 AUC（12-24/12h）、FEV1 AUC（0-24/24h）、早晨预剂量 FEV1、峰值 FEV1 和 COPD 症状评分从基线的变化。
30 名 COPD 患者被随机分组，27 名患者完成了研究。第 15 天，阿地溴铵和噻托溴铵与安慰剂相比，FEV1 AUC（0-12/12h）从基线的平均变化显著更大（P<.0001）。第 15 天，FEV1 AUC（12-24/12h）、FEV1 AUC（0-24/24h）、早晨预剂量 FEV1 和峰值 FEV1 的变化与安慰剂相比，阿地溴铵和噻托溴铵均显著更大（除 FEV1 AUC（12-24/12h）噻托溴铵与安慰剂相比 P<.001 外，所有 P<.0001）。在所有正常化 FEV1 AUC 值中，阿地溴铵的数值在第 1 天，在 FEV1 AUC（12-24/12h）在第 15 天，与噻托溴铵相比，阿地溴铵的改善均显著大于噻托溴铵（所有 P<.05）。与安慰剂相比，阿地溴铵治疗可显著改善 COPD 症状（P<.05），但噻托溴铵则无此作用。
在 COPD 患者中，与安慰剂相比，阿地溴铵 400μg bid 提供了具有临床意义的 24 小时支气管扩张改善，通常与噻托溴铵 18μg 每日一次相当，但阿地溴铵在平均夜间时段具有显著的优势。正在进行更大规模、更长治疗时间的研究，以证实阿地溴铵 400μg bid 对支气管扩张和 COPD 症状的疗效。
ClinicalTrials.gov；编号：NCT00868231；网址：www.clinicaltrials.gov。
