A FIM study to assess safety and exposure of inhaled single doses of AP301-A specific ENaC channel activator for the treatment of acute lung injury.
A FIM study to assess safety and exposure of inhaled single doses of AP301-A specific ENaC channel activator for the treatment of acute lung injury.
复制标题
DOI：
10.1002/jcph.203
复制
发表时间：
2014-03
影响因子：
2.9
通讯作者：
Hermann, Robert
中科院分区：
文献类型：
--
作者：
Schwameis, Richard;Eder, Sandra;Pietschmann, Helmut;Fischer, Bernhard;Mascher, Hermann;Tzotzos, Susan;Fischer, Hendrik;Lucas, Rudolf;Zeitlinger, Markus;Hermann, Robert
AP 301是ENaC介导的Na+摄取的激活剂，用于治疗急性呼吸窘迫综合征（ARDS）中的肺渗透性水肿。这项“首次人体”研究的目的是检查健康男性受试者吸入单次剂量递增的AP 301的局部和全身安全性以及全身暴露量。在一项双盲、安慰剂对照研究中，48例健康男性受试者被随机分配至6个递增剂量组（单次给药最高达120 mg），每组8例受试者（AP 301：安慰剂3：1随机分配）。系列评估包括肺活量测定、呼出一氧化氮（eNO）、生命体征、ECG、安全性实验室检查、不良事件（AE）和用于定量血浆中AP 301的血样。采用描述性统计。所有48例受试者均接受了治疗，并按照方案完成了研究。无严重、局部（例如，声嘶、咳嗽、支气管痉挛）或剂量限制性AE。所有评估均未显示安全性结局的显著剂量或时间相关变化。观察到的AP 301全身暴露水平非常低，最高剂量组的平均Cmax值<2.5 ng/mL。健康男性受试者吸入高达120 mg的AP 301单次给药安全且耐受性良好。吸入性AP 301的分布主要局限于肺部，如非常低的AP 301全身暴露水平所示。
AP301 is an activator of ENaC-mediated Na+ uptake for the treatment of pulmonary permeability edema in acute respiratory distress syndrome (ARDS). The purpose of this “first-in-man” study was to examine local and systemic safety and systemic exposure of ascending single doses of AP301, when inhaled by healthy male subjects. In a double-blind, placebo-controlled study, 48 healthy male subjects were randomized to 6 ascending dose groups (single doses up to 120 mg) of 8 subjects each (3:1 randomization of AP301: placebo). Serial assessments included spirometry, exhaled nitric oxide (eNO), vital signs, ECG, safety laboratory, adverse events (AE), and blood samples for the quantification of AP301 in plasma. Descriptive statistics was applied. All 48 subjects received treatment, and completed the study as per protocol. No serious, local (e.g., hoarseness, cough, bronchospasm), or dose-limiting AEs were noted. None of the assessments indicated notable dose or time-related alterations of safety outcomes. Observed AP301 systemic exposure levels were very low, with mean Cmax values of <2.5 ng/mL in the highest dose groups. Inhaled AP301 single doses up to 120 mg were safe and well tolerated by healthy male subjects. Distribution of inhaled AP301 was largely confined to the lung, as indicated by very low AP301 systemic exposure levels.
登录
查看更多内容
影响因子：
4
作者：
Xiong, Chenling;Yang, Guang;Kumar, Sanjiv;Aggarwal, Saurabh;Leustik, Martin;Snead, Connie;Hamacher, Juerg;Fischer, Bernhard;Umapathy, Nagavedi S.;Hossain, Hamid;Wendel, Albrecht;Catravas, John D.;Verin, Alexander D.;Fulton, David;Black, Stephen M.;Chakraborty, Trinad;Lucas, Rudolf
通讯作者：
Lucas, Rudolf
影响因子：
4.8
作者：
Lee, Jae W.;Fang, Xiaohui;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
DOI：
10.1164/rccm.200406-710st
发表时间：
2005-04-15
影响因子：
24.7
作者：
American Thoracic Society;European Respiratory Society
通讯作者：
European Respiratory Society
影响因子：
4
作者：
Penel, Nicolas;Kramar, Andrew
通讯作者：
Kramar, Andrew
影响因子：
3.8
作者：
LEWIS, TR;MORROW, PE;CHHABRA, RS
通讯作者：
CHHABRA, RS