DENUFOSOL TETRASODIUM INHALATION SOLUTION IN PATIENTS WITH MILD CF LUNG DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 囊性纤维化（CF）是一种隐性遗传性疾病，以肺和鼻窦疾病以及胃肠道和生殖道功能障碍为特征。这种疾病是由囊性纤维化跨膜调节因子（CFTR）基因突变引起的，该基因编码一种顶端膜上皮蛋白，其功能是c-AMP调节的氯离子通道和其他通道的调节因子。缺陷性CFTR导致异常离子转运和耗尽的气道表面液体体积，伴随粘膜纤毛清除率降低和呼吸道慢性感染的倾向，导致炎症、进行性气道损伤和支气管扩张。CF患者遭受肺部细菌定植、肺部加重和慢性肺功能下降的慢性重复周期，这常常导致过早死亡。 Denufosol tetrasylate（INS 37217）吸入溶液（denufosol）是InspirePharmaceuticals，Inc.正在开发的一种选择性P2 Y2受体激动剂。地努福索可能具有在CF肺病过程中相对早期恢复或维持患者的粘膜纤毛清除的能力。这项多中心、随机、双盲、安慰剂对照的3期研究将在相对健康的CF患者人群中检查地努福索作为早期干预治疗，相对于安慰剂改善肺功能。符合条件的患者将随机接受denufosol 60 mg或安慰剂，每日3次，治疗24周。

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 a recessive genetic disease, characterized by pulmonary and sinus disease, and gastrointestinal and reproductive tract dysfunction. The disease is caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, which encodes for an apical membrane epithelial protein that functions as a c-AMP-regulated chloride channel and a regulator of other channels. Defective CFTR results in abnormal ion transport and depleted airway surface liquid volume with reduced mucociliary clearance and a propensity for chronic infection of the respiratory tract with resulting inflammation, progressive airway damage and bronchiectasis. CF patients suffer from chronic repeated cycles of pulmonary bacterial colonization, pulmonary exacerbations and chronic lung function decline, which often lead to premature death. Denufosol tetrasodium (INS37217) inhalation solution (denufosol) is a selective P2Y2 receptor agonist under development by InspirePharmaceuticals, Inc. Denufosol may have the ability to restore or maintain mucociliary clearance in patients relatively early in the CF lung disease process. This multicenter, randomized, double-blind, placebo-controlled Phase 3 study will examine denufosol as an early intervention therapy to improve lung function relative to placebo in a relatively healthy CF patient population. Eligible patients will be randomized to receive either denufosol 60 mg or placebo three times daily for a 24-week treatment period.