Ferguson Gary T, Feldman Gregory, Pudi Krishna K, Barnes Chris N, Moran Edmund J, Haumann Brett, Pendyala Srikanth, Crater Glenn
Pulmonary Research Institute of Southeast Michigan, Farmington Hills.
South Carolina Pharmaceutical Research, Spartanburg.
Chronic Obstr Pulm Dis. 2019 Apr 9;6(2):154-165. doi: 10.15326/jcopdf.6.2.2018.0152.
Revefenacin, a novel, lung-selective, long-acting muscarinic antagonist, has been developed for nebulized therapy for chronic obstructive pulmonary disease (COPD). We present the results of replicate Phase III efficacy and safety studies of revefenacin in patients with moderate to very severe COPD.
In 2 double-blind, parallel-group studies, (Study 0126 and Study 0127), patients ≥ 40 years old were randomized to revefenacin 88 μg, revefenacin 175 μg or placebo administered once daily by standard jet nebulizer for 12 weeks. The primary endpoint was 24-hour trough forced expiratory volume in 1 second (FEV) on day 85. Secondary efficacy endpoints included overall treatment effect (OTE) on trough FEV and peak FEV (0-2 hours after first dose). Safety assessments included treatment-emergent adverse events.
At day 85, revefenacin 88 µg and 175 µg improved trough FEV versus placebo in Study 0126 (by 79 mL [=0.0003] and 146 mL [<0.0001]) and Study 0127 (by 160 mL and 147 mL; both <0.0001). Compared with placebo, pooled data of revefenacin 88 µg and 175 µg increased OTE trough FEV by 115 mL and 142 mL (both <0.001) and increased peak FEV by 127 mL and 129 mL (both <0.0001). Revefenacin 175 µg demonstrated greater improvements in FEV in concomitant long-acting beta2-agonist patients and in more severe patients than revefenacin 88 µg. Adverse events were minor.
Revefenacin, administered once daily for 12 weeks to patients with moderate to very severe COPD, demonstrated clinically significant improvements in trough FEV and OTE FEV. Revefenacin was generally well tolerated with no major safety concerns.
瑞呋芬那新是一种新型的、肺选择性、长效毒蕈碱拮抗剂，已被开发用于慢性阻塞性肺疾病（COPD）的雾化治疗。我们展示了瑞呋芬那新在中度至重度COPD患者中的重复III期疗效和安全性研究结果。
在2项双盲、平行组研究（研究0126和研究0127）中，年龄≥40岁的患者被随机分为接受88μg瑞呋芬那新、175μg瑞呋芬那新或安慰剂治疗，通过标准喷射雾化器每日给药1次，持续12周。主要终点是第85天的24小时谷值1秒用力呼气量（FEV）。次要疗效终点包括对谷值FEV和峰值FEV（首剂后0 - 2小时）的总体治疗效果（OTE）。安全性评估包括治疗中出现的不良事件。
在第85天，研究0126中88μg和175μg瑞呋芬那新组的谷值FEV较安慰剂组有所改善（分别提高79 mL [=0.0003]和146 mL [<0.0001]），研究0127中分别提高160 mL和147 mL（均<0.0001）。与安慰剂相比，88μg和175μg瑞呋芬那新的汇总数据使OTE谷值FEV分别增加115 mL和142 mL（均<0.001），使峰值FEV分别增加127 mL和129 mL（均<0.0001）。与88μg瑞呋芬那新相比，175μg瑞呋芬那新在合并使用长效β2激动剂的患者和病情更严重的患者中，FEV改善更明显。不良事件轻微。
对中度至重度COPD患者每日给药1次，持续12周的瑞呋芬那新，在谷值FEV和OTE FEV方面显示出具有临床意义的改善。瑞呋芬那新总体耐受性良好，无重大安全问题。
