DENUFOSOL TETRASODIUM INHALATION SOLUTION IN PATIENTS WITH CF LUNG DISEASE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。囊性纤维化（CF）的特征在于慢性气道阻塞和感染。在CF中，水、钠离子和氯离子的运输是异常的。这导致气道分泌物变稠，阻塞气道，使患者更容易患慢性细菌感染。初步研究表明，针对这种离子转运异常的治疗可能是有益的。INS 37217是一种化合物，可以改善氯离子和水从气道细胞中的转运，从而使分泌物水合并使其更容易咳嗽出来。此外，INS 37217使纤毛更频繁地跳动，这可能会提高身体清除肺部分泌物的能力。本研究是一项多中心、双盲、随机、安慰剂对照、平行组试验，在轻度至中度囊性纤维化肺病受试者中比较两种剂量水平的INS 37217吸入溶液与安慰剂通过PARI LC星星雾化器给药28天的安全性和疗效。将入组72例受试者，3个治疗组各约24例受试者。在治疗期间，受试者将以1：1：1的比例随机分配至3个治疗组之一，接受4 mL 5 mg/mL（20 mg）、15 mg/mL（60 mg）INS 37217或4 mL安慰剂（0. 9% w/v无菌氯化钠溶液）给药。将根据筛选时肺功能（FEV 1 75%预测值）和长期使用TOBI？（是vs.否）对随机化进行分层。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystic Fibrosis (CF) is characterized by chronic airways blockage and infection. In CF, the transport of water, sodium ions, and chloride ions is abnormal. This results in thickened airway secretions that obstruct airways and make patients more likely to get chronic bacterial infections. Preliminary studies suggest that therapy targeted to this abnormality in ion transport may be beneficial. INS37217 is a compound that may improve transport of chloride and water out of airway cells, therefore hydrating secretions and making them easier to cough out. In addition, INS37217 makes the cilia beat more frequently, which may improve the body's ability to clear secretions out of the lung. This study is a multi-center, double-blind, randomized, placebo-controlled, parallel-group trial comparing the safety and efficacy of two dose levels of INS37217 Inhalation Solution to placebo administered over 28 days via the PARI LC STAR¿ nebulizer in subjects with mild to moderate cystic fibrosis lung disease. Seventy-two subjects will be enrolled with approximately 24 subjects in each of three treatment groups Subjects will be randomly assigned in a 1:1:1 ratio to one of three treatment arms delivered in 4 mL of 5 mg/mL (20 mg), 15 mg/mL (60 mg) INS37217 or 4 mL of placebo (0.9% w/v solution of sterile sodium chloride) for the duration of the treatment period. Randomization will be stratified on the basis of screening lung function (FEV1 75% of predicted) and chronic TOBI¿ use (yes vs. no).