Data from: Efficacy and safety of four weeks’ treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial

BACKGROUND: Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting β2 agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma. TRIAL DESIGN: A multicentre, randomised, double-blind, parallel-group, placebo-controlled study. METHODS: Participants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 μg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 μg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0–4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV1) (23–24 h postdose; day 29) and wm FEV1 (0–4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 μg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment. RESULTS: 60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV1 per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0–4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI −3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV1 (mean difference 183 ml) and 0–4 h postdose wm FEV1 (mean difference 236 ml). CONCLUSION: FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD.背景：糠酸氟替卡松/维兰特罗（Fluticasone furoate/vilanterol, FF/VI）是一款处于研发阶段的新型每日一次（once-daily, OD）吸入性糖皮质激素（inhaled corticosteroid）/长效β₂受体激动剂（long-acting β2 agonist）复方制剂，用于慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）与哮喘的治疗。试验设计：一项多中心、随机、双盲、平行组、安慰剂对照研究。研究方法：受试者为中度至重度慢性阻塞性肺疾病患者，分别接受安慰剂或FF/VI 400/25 μg 每日一次给药，疗程共4周。本研究旨在评估通过新型干粉吸入器（dry powder inhaler）给药的FF/VI 400/25 μg 每日一次、给药4周的安全性与有效性。共同主要终点为第28天给药后0~4小时的加权平均（weighted mean, wm）心率较基线的变化值，以及不良事件（adverse events, AEs）的发生率。次要终点包括第29天给药后23~24小时的一秒钟用力呼气容积（forced expiratory volume in one second, FEV1）谷值较基线的变化值，以及第28天给药后0~4小时的加权平均FEV1较基线的变化值。受试者以2:1的比例随机分配至FF/VI组或安慰剂组；所有受试者与研究人员均对治疗分组（活性药物或安慰剂）设盲。研究结果：共计60例患者（平均年龄64岁）完成随机分组（FF/VI组：n=40；安慰剂组：n=20），所有受试者的数据均纳入分析。两组患者基线时的支气管舒张后FEV1占预计值百分比无显著差异（FF/VI组：58.5%；安慰剂组：60.1%）。两组给药后0~4小时的加权平均心率相近，组间差值为0.6次/分钟（95%置信区间：-3.9~5.1）。FF/VI组报告的治疗期间不良事件发生率（68%）高于安慰剂组（50%）。FF/VI组最常见的药物相关不良事件为口腔念珠菌病（8%）与发音困难（5%）。本研究未观察到对实验室指标（包括血糖与血钾）、生命体征或心电图/动态心电图（Holters）具有临床意义的影响。相较于安慰剂组，FF/VI组的FEV1谷值（平均差值183 ml）与给药后0~4小时加权平均FEV1（平均差值236 ml）均较基线出现具有统计学意义的改善。研究结论：FF/VI具有良好的安全性与耐受性，相较于安慰剂可改善慢性阻塞性肺疾病患者的肺功能。