Navafenterol (AZD8871) belongs to a new class of bronchodilator, the single-molecule muscarinic antagonist and β-agonist, developed for the treatment of COPD. This study aimed to evaluate the efficacy, pharmacokinetics and safety of navafenterol versus placebo and an active comparator treatment for moderate-to-severe COPD.

This phase 2a, randomised, multicentre (Germany and UK), double-blind, double-dummy, three-way complete crossover study (ClinicalTrials.gov identifier: NCT03645434) compared 2 weeks’ treatment of once-daily navafenterol 600 µg via inhalation with placebo and a fixed-dose combination bronchodilator (umeclidinium/vilanterol (UMEC/VI); 62.5 µg/25 µg) in participants with moderate-to-severe COPD. The primary outcome was change from baseline in trough forced expiratory volume in 1 s (FEV₁) on day 15. Secondary end-points included change from baseline in peak FEV₁; change from baseline in Breathlessness, Cough and Sputum Scale (BCSS); change from baseline in COPD Assessment Tool (CAT); adverse events; and pharmacokinetics.

73 participants were randomised. After 14 days, trough FEV₁ was significantly improved with navafenterol compared with placebo (least-squares (LS) mean difference 0.202 L; p<0.0001). There was no significant difference in FEV₁ between navafenterol and UMEC/VI (LS mean difference –0.046 L; p=0.075). COPD symptoms (CAT and BCSS) showed significantly greater improvements with both active treatments versus placebo (all p<0.005). Novel objective monitoring (VitaloJAK) showed that cough was reduced with both active treatments compared with placebo. Safety profiles were similar across the treatment groups and no serious adverse events were reported in the navafenterol treatment period.

Once-daily navafenterol was well tolerated, improved lung function and reduced COPD-related symptoms, similar to an established once-daily fixed-dose combination bronchodilator.

Navafenterol (AZD8871) 属于一类新型支气管扩张剂，是一种单分子毒蕈碱拮抗剂和 β-激动剂，用于治疗 COPD。本研究旨在评估纳伐芬特罗与安慰剂和活性比较剂治疗中度至重度 COPD 的疗效、药代动力学和安全性。

这项 2a 期、随机、多中心（德国和英国）、双盲、双模拟、三向完全交叉研究（ClinicalTrials.gov 标识符：NCT03645434）比较了 2 周每天一次吸入 600 µg 纳伐芬特罗与安慰剂和固定剂量联合支气管扩张剂（umeclidinium/vilanterol (UMEC/VI)；62.5 µg/25 µg）用于中度至重度 COPD 的参与者。主要结果是第 15 天 1 秒内用力呼气量 (FEV ₁ ) 与基线相比的变化。次要终点包括 FEV ₁峰值与基线相比的变化；呼吸困难、咳嗽和痰量表 (BCSS) 的基线变化；从 COPD 评估工具 (CAT) 中的基线变化；不良事件; 和药代动力学。

73 名参与者被随机分配。14 天后，与安慰剂相比，纳伐芬特罗的 FEV ₁谷值显着改善（最小二乘 (LS) 均值差 0.202 L；p<0.0001）。_{纳伐芬特罗和 UMEC/VI 之间的 FEV 1}没有显着差异（LS 平均差 –0.046 L；p=0.075）。COPD 症状（CAT 和 BCSS）显示出与安慰剂相比，积极治疗显着改善（所有 p<0.005）。新的客观监测 (VitaloJAK) 表明，与安慰剂相比，两种积极治疗的咳嗽都减少了。各治疗组的安全性相似，在纳伐芬特罗治疗期间未报告严重不良事件。

每日一次的纳伐芬特罗耐受性良好，改善了肺功能并减少了 COPD 相关症状，类似于已确定的每日一次固定剂量组合支气管扩张剂。