Design of the INPULSIS™ trials: Two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis
Design of the INPULSIS™ trials: Two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis
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DOI：
10.1016/j.rmed.2014.04.011
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发表时间：
2014-07-01
影响因子：
4.3
通讯作者：
Collard, Harold R.
中科院分区：
文献类型：
--
作者：
Richeldi, Luca;Cottin, Vincent;Collard, Harold R.
背景：Nursing作为特发性肺纤维化（IPF）的治疗药物正在临床开发中。II期TOMORROW研究的数据表明，尼达尼布150 mg每日两次具有临床益处，且安全性可接受。方法：INPULSIS（TM）试验是重复的III期、随机、双盲研究，比较尼达尼布150 mg每日两次与安慰剂在IPF患者中的疗效和安全性。符合条件的患者年龄≥ 40岁，随机化前5年内诊断为IPF，筛选前1年内接受过胸部高分辨率计算机断层扫描（HRCT），用力肺活量（FVC）>=50%预测值，一氧化碳弥散量为30-79%预测值。受试者以3：2的比例随机接受尼达尼布或安慰剂治疗52周。主要终点是FVC的年下降率。关键次要终点是52周内圣乔治呼吸问卷（一种健康相关生活质量的衡量指标）总评分较基线的变化以及首次急性加重的时间。结果将于2014年上半年报告。结论：INPULSIS（TM）试验将确定尼达尼布在IPF患者中的疗效，包括其对疾病进展（定义为FVC下降）、急性加重和健康相关生活质量的影响。此外，他们将评估尼达尼布在该患者人群中的不良事件特征。试验注册：在ClinicalTrials.gov注册（标识符：NCT 01335464和NCT 01335477）。(C)2014作者由Elsevier Ltd.发布。这是CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/3.0/）。
Background: Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF). Data from the Phase II TOMORROW study suggested that nintedanib 150 mg twice daily had clinical benefits with an acceptable safety profile.Methods: The INPULSIS (TM) trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150 mg twice daily with placebo in patients with IPF. Eligible patients were aged >=40 years with a diagnosis of IPF within 5 years before randomization who had undergone a chest high-resolution computed tomography (HRCT) scan within 1-year before screening, and who had a forced vital capacity (FVC) of >=50% predicted and a diffusing capacity for carbon monoxide of 30-79% predicted. Participants were randomized 3:2 to receive nintedanib or placebo for 52 weeks. The primary endpoint is the annual rate of decline in FVC. The key secondary endpoints are change from baseline in the total score on the St. George's Respiratory Questionnaire (a measure of health-related quality of life) over 52 weeks and time to first acute exacerbation.Results: Enrolment of 1066 patients in 24 countries was completed in September 2012. Results will be reported in the first half of 2014.Conclusion: The INPULSIS (TM) trials will determine the efficacy of nintedanib in patients with IPF, including its impact on disease progression as defined by decline in FVC, acute exacerbations and health-related quality of life. In addition, they will characterise the adverse event profile of nintedanib in this patient population.Trial registration: Registered at ClinicalTrials.gov (identifiers: NCT01335464 and NCT01335477). (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).