Unit of Respiratory Clinical Pharmacology, Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.
Clin Drug Investig. 2012 Mar 1;32(3):147-55. doi: 10.2165/11630880-000000000-00000.
Bronchodilator therapy is central to the symptomatic management of chronic obstructive pulmonary disease (COPD), and treatment with short-acting bronchodilators is recommended in patients with mild COPD.
This study aimed to evaluate the onset of effect of single-dose formoterol 9 μg versus single-dose salmeterol 50 μg in patients with moderate COPD.
In this multicentre, double-blind, double-dummy, placebo-controlled, three-way single-dose crossover study, patients ≥40 years of age with moderate COPD were randomized to single-dose formoterol 9 μg via Turbuhaler® plus placebo via Diskus®, single-dose salmeterol 50 μg via Diskus® plus placebo via Turbuhaler® or placebo via Turbuhaler® and Diskus® (washout period 2-7 days). Terbutaline 0.5 mg/actuation via Turbuhaler® was used as reliever medication throughout. The primary endpoint was forced expiratory volume in 1 second (FEV₁) at 5 minutes post-dose. Secondary endpoints included proportion of patients achieving ≥12% increase in FEV₁ at 5 minutes post-dose.
109 patients were randomized, and 108 completed the study. The increase in FEV₁ 5 minutes post-dose versus pre-dose was 7.2% for formoterol, 4.1% for salmeterol and 0.7% for placebo, and significantly greater for formoterol versus salmeterol (ratio of treatment effects: 1.030; 95% CI 1.008, 1.052; p = 0.009), for formoterol versus placebo (1.064, 95% CI 1.041, 1.087; p < 0.001) and for salmeterol versus placebo (1.033, 95% CI 1.011, 1.056; p = 0.003). The proportions of patients with ≥12% increase in FEV₁ 5 minutes post-dose were 23.1%, 9.2% and 6.4% for formoterol, salmeterol and placebo, respectively; this was statistically significantly larger after formoterol than salmeterol (p = 0.008) or placebo (p < 0.001). All treatments were well tolerated.
In COPD patients, formoterol 9 μg has an onset of bronchodilatory effect that is more rapid than salmeterol 50 μg based on FEV₁ at 5 minutes post-dose.
Clinicaltrials.gov identifier: NCT01048333; AstraZeneca study code: D5127C00001.
支气管扩张剂疗法是慢性阻塞性肺疾病（COPD）症状管理的核心，对于轻度 COPD 患者推荐使用短效支气管扩张剂治疗。
本研究旨在评估中重度 COPD 患者单次应用福莫特罗 9μg 与沙美特罗 50μg 的起效时间。
这是一项多中心、双盲、双模拟、安慰剂对照的三交叉、单次剂量研究，纳入≥40 岁的中重度 COPD 患者，随机接受福莫特罗 9μg 经 Turbuhaler® 吸入装置给药+安慰剂经 Diskus® 吸入装置给药、沙美特罗 50μg 经 Diskus® 吸入装置给药+安慰剂经 Turbuhaler® 吸入装置给药或安慰剂经 Turbuhaler® 和 Diskus® 给药（洗脱期 2-7 天）。研究全程使用特布他林 0.5mg/吸经 Turbuhaler® 作为缓解药物。主要终点为单次给药后 5 分钟时的第 1 秒用力呼气量（FEV₁）。次要终点包括单次给药后 5 分钟时 FEV₁ 增加≥12%的患者比例。
109 名患者被随机分组，108 名患者完成了研究。与基线相比，福莫特罗、沙美特罗和安慰剂给药后 5 分钟时的 FEV₁ 增加值分别为 7.2%、4.1%和 0.7%，福莫特罗的增加显著大于沙美特罗（治疗效果比值：1.030；95%置信区间 1.008，1.052；p=0.009），福莫特罗与安慰剂（1.064；95%置信区间 1.041，1.087；p<0.001），沙美特罗与安慰剂（1.033；95%置信区间 1.011，1.056；p=0.003）。福莫特罗、沙美特罗和安慰剂给药后 5 分钟时 FEV₁ 增加≥12%的患者比例分别为 23.1%、9.2%和 6.4%；福莫特罗显著大于沙美特罗（p=0.008）或安慰剂（p<0.001）。所有治疗均耐受良好。
基于给药后 5 分钟的 FEV₁，福莫特罗 9μg 起效时间快于沙美特罗 50μg，在 COPD 患者中具有更快的支气管扩张作用。
ClinicalTrials.gov 标识符：NCT01048333；阿斯利康研究代码：D5127C00001。
