糠酸氟替卡松/维兰特罗（50/25微克；100/25微克；200/25微克）在亚洲慢性阻塞性肺疾病患者中的疗效和安全性：一项随机安慰剂对照试验
Efficacy and safety of fluticasone furoate/vilanterol (50/25 mcg; 100/25 mcg; 200/25 mcg) in Asian patients with chronic obstructive pulmonary disease: a randomized placebo-controlled trial.
作者信息
Zheng Jinping, de Guia Teresita, Wang-Jairaj Jie, Newlands Amy H, Wang Changzheng, Crim Courtney, Zhong Nanshan
机构信息
State Key Lab of Respiratory Disease, National Clinical Research Centre of Respiratory Disease, 1st Affiliated Hospital of Guangzhou Medical University , Guangzhou , China.
出版信息
Curr Med Res Opin. 2015 Jun;31(6):1191-200. doi: 10.1185/03007995.2015.1036016.
BACKGROUND AND OBJECTIVE
Three strengths of fluticasone furoate/vilanterol (FF/VI) were previously evaluated for the treatment of chronic obstructive pulmonary disease (COPD) in a program of global Phase 3 studies that included only a small subgroup of Asian patients. This study further evaluated the efficacy and safety of the same three strengths of FF/VI exclusively in Asian patients.
METHODS
A randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Patients with post-bronchodilator FEV1/FVC ≤0.70, FEV1 ≤70% predicted and modified Medical Research Council score ≥2 were randomized (1:1:1:1) to placebo, FF/VI 50/25 mcg, 100/25 mcg or 200/25 mcg once daily via the ELLIPTA dry powder inhaler. The primary efficacy endpoint was change from baseline in trough FEV1 at Week 24.
RESULTS
The intent-to-treat population comprised 643 patients. Statistically significant (p < 0.001) improvements in trough FEV1 were observed with all strengths of FF/VI versus placebo at Week 24 (0.14-0.19 L). Reduction of supplemental albuterol use was observed with all strengths of FF/VI versus placebo. The incidence of on-treatment adverse events (AEs) was 48% with FF/VI 200/25 mcg and 37-40% with other treatments. The incidence of on-treatment serious AEs was 4-9% with FF/VI treatments versus 9% with placebo; however, the study only covered a 6 month treatment period and was not powered to assess effects on exacerbations. No clinically significant treatment effects versus placebo were identified for electrocardiogram, vital signs, 24 hour urinary cortisol excretion and pneumonia.
CONCLUSIONS
All strengths of FF/VI improved lung function with an acceptable safety profile. There is no evidence to suggest that dose adjustment may be required in Asian patients using FF/VI 100/25 mcg for the treatment of COPD.
CLINICAL TRIAL REGISTRATION
NCT01376245.
背景与目的
糠酸氟替卡松/维兰特罗（FF/VI）的三种剂量强度先前已在一项全球3期研究计划中进行了评估，该计划用于治疗慢性阻塞性肺疾病（COPD），但其中仅纳入了一小部分亚洲患者亚组。本研究进一步专门在亚洲患者中评估了相同三种剂量强度的FF/VI的疗效和安全性。
方法
一项随机、双盲、安慰剂对照、平行组、多中心研究。支气管扩张剂后FEV1/FVC≤0.70、FEV1≤预测值的70%且改良医学研究委员会评分≥2的患者，通过ELLIPTA干粉吸入器随机（1:1:1:1）分配至安慰剂组、FF/VI 50/25μg组、100/25μg组或200/25μg组，每日一次。主要疗效终点为第24周时谷值FEV1相对于基线的变化。
结果
意向性治疗人群包括643例患者。在第24周时，与安慰剂相比，所有剂量强度的FF/VI均观察到谷值FEV1有统计学意义的改善（p<0.001）（改善幅度为0.14 - 0.19L）。与安慰剂相比，所有剂量强度的FF/VI均观察到沙丁胺醇补充使用量减少。FF/VI 200/25μg组治疗期间不良事件（AE）的发生率为48%，其他治疗组为37 - 40%。FF/VI各治疗组治疗期间严重AE的发生率为4 - 9%，安慰剂组为9%；然而，该研究仅涵盖6个月的治疗期，未设定评估对病情加重影响的效力。在心电图、生命体征、24小时尿皮质醇排泄和肺炎方面，未发现与安慰剂相比有临床显著的治疗效果。
结论
所有剂量强度的FF/VI均改善了肺功能，且安全性可接受。没有证据表明使用FF/VI 100/25μg治疗COPD的亚洲患者可能需要调整剂量。
临床试验注册号
NCT01376245
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