In patients with chronic obstructive pulmonary disease (COPD) classified as moderate onwards, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines recommend regular treatment with one or more long-acting bronchodilators, such as beta(2)-agonists or anticholinergics. In contrast to currently available long-acting beta(2)-agonists, which have a duration of action of 12 h, indacaterol has demonstrated effective 24-h bronchodilation on once-daily dosing. A double-blind, randomised, placebo-controlled study was conducted to compare the safety, tolerability and efficacy of indacaterol with that of placebo, over a 28-day period, in patients with moderate COPD (as defined by GOLD 2001 criteria; equivalent to moderate-to-severe COPD in the GOLD 2005 criteria). Patients were randomised 2:2:1 to receive indacaterol 400 microg or 800 microg or placebo once-daily (between 07:00 and 11:00 h) via a single-dose dry-powder inhaler for 28 days. Assessments included monitoring of adverse events (AEs), blood chemistry (including serum potassium and blood glucose), vital signs (blood pressure and heart rate), electrocardiograms and spirometry. One hundred and sixty-three patients were randomised, with 155 (95%) completing the study. There were no statistically significant differences between treatment groups in the overall incidence of AEs, with AEs reported by 35%, 51% and 25% of patients in the indacaterol 400 microg, 800 microg and placebo groups, respectively. The majority of AEs were mild or moderate in severity, and there were no study-drug related serious AEs. There were no statistically significant differences between indacaterol groups and placebo in mean pulse rate and QTc interval, and isolated statistically significant (p<0.05) treatment-placebo differences in mean blood pressure, blood glucose and serum potassium. There was a statistically significant improvement in FEV(1) vs placebo at all post-baseline timepoints for both indacaterol treatment groups; 30 min post-dose, adjusted mean+/-SE FEV(1) indacaterol-placebo differences were: Day 1, 220+/-36 ml and 210+/-36 ml; Day 14, 320+/-50 ml and 270+/-50 ml; Day 28, 260+/-61 ml and 200+/-61 ml for 400 and 800 microg, respectively (all p<0.01 vs placebo). Bronchodilation was still apparent after 24h, with pre-dose (i.e. trough) adjusted mean+/-SE FEV(1) indacaterol-placebo differences of: Day 14, 230+/-44 ml and 210+/-44 ml; Day 28, 220+/-49 ml and 210+/-49 ml for indacaterol 400 and 800 microg, respectively (all p<0.0001 vs placebo). Once-daily indacaterol was well tolerated at doses up to 800 microg with a good overall safety profile. There was no statistical difference at any dose between the safety of indacaterol and placebo. Furthermore, this study supports the previously demonstrated 24-h bronchodilator efficacy of indacaterol.

译文

:对于慢性阻塞性肺疾病(COPD)被归类为中度以上的患者,《全球慢性阻塞性肺疾病倡议(GOLD)指南》建议定期使用一种或多种长效支气管扩张药,例如β(2)-激动剂或抗胆碱药。与目前可用的长效β(2)激动剂(作用持续时间为12小时)相反,茚达特罗已证明每天一次给药有效的24小时支气管扩张作用。进行了一项双盲,随机,安慰剂对照研究,比较了茚达特罗和安慰剂在中度COPD患者(在28天之内)的安全性,耐受性和疗效(按GOLD 2001标准定义;相当于GOLD 2005标准中的中度至重度COPD)。患者被随机以2:2:1的比例通过单剂量干粉吸入器每天一次(07:00至11:00 h)接受400毫克或800毫克茚达特罗或安慰剂治疗28天。评估包括监测不良事件(AE),血液化学(包括血清钾和血糖),生命体征(血压和心率),心电图和肺活量测定法。 163名患者被随机分配,其中155名(95%)完成了研究。在治疗组之间,AEs的总发生率没有统计学上的显着差异,在茚达特罗400微克,800微克和安慰剂组中,分别有35%,51%和25%的患者报告了AEs。大多数不良事件的严重程度为轻度或中度,并且没有与研究药物相关的严重不良事件。茚达特罗组与安慰剂之间在平均脉搏率和QTc间隔方面无统计学意义上的差异,并且隔离治疗组与安慰剂之间的平均血压,血糖和血清钾差异也有统计学意义(p <0.05)。两个茚达特罗治疗组在所有基线后时间点,FEV(1)均较安慰剂有统计学上的显着改善;给药后30分钟,调整后的均值/ -SE FEV(1)茚达特罗-安慰剂的差异为:第1天,220 / -36 ml和210 / -36 ml;第14天,320 / -50毫升和270 / -50毫升;第28天,分别为260 / -61 ml和200 / -61 ml,分别用于400和800 microg(相对于安慰剂,所有p <0.01)。 24小时后仍明显支气管扩张,给药前(即波谷)调整后的均值/ SE FEV(1)茚达特罗-安慰剂的差异为:第14天,230 / -44毫升和210 / -44毫升;第28天,茚达特罗400和800微克分别为220 / -49毫升和210 / -49毫升(相对于安慰剂,所有p <0.0001)。每日一次茚达特罗在800微克的剂量下具有良好的耐受性,并且具有良好的总体安全性。茚达特罗和安慰剂的安全性在任何剂量下均无统计学差异。此外,这项研究支持了茚达特罗先前证明的24小时支气管扩张药疗效。

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