EFFICACY AND SAFETY OF DENUFOSOL TETRASODIUM (INS37217) INHALATION SOLUTION

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。 基于对囊性纤维化的病理生理学的了解，正在开发用于治疗囊性纤维化的新疗法。P2 Y2受体激动剂代表了一种治疗CF的新方法，其试图绕过气道上皮中有缺陷的CFTR，而是利用这类药物对不依赖于CFTR的粘膜纤毛清除的综合作用。这些药剂通过刺激P2 Y2受体起作用，这导致氯离子（Cl-）和液体分泌以及抑制钠（Na+）吸收以水合气道表面液体层并产生更正常的纤毛周围流体环境，同时还刺激杯状细胞的粘蛋白分泌并增加纤毛搏动频率。 Denufosol tetrasylate（INS 37217）吸入溶液（denufosol）是一种新型第二代、化学稳定、选择性P2 Y2受体激动剂，正在由Ampire Pharmaceuticals，Inc.开发。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，这可能保护肺功能并减少肺细菌定植、肺恶化和慢性肺功能下降的不可避免的重复周期。 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。在本研究的24周安慰剂对照部分完成时，所有患者将在安全性延长期内接受60 mg地纽福索，每日三次，持续额外的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. New therapies are being developed for the treatment of cystic fibrosis, based on insights into the pathophysiology of the disease. P2Y2 receptor agonists represent a novel approach to the treatment of CF that attempts to bypass defective CFTR in airway epithelia and, instead, take advantage of the integrated actions of this class of agents on mucociliary clearance that are not dependent on CFTR. These agents act by stimulating the P2Y2 receptor, which results in chloride ion (Cl-) and liquid secretion and the inhibition of sodium (Na+) absorption to hydrate the airway surface liquid layer and create a more normal periciliary fluid milieu, while also stimulating mucin secretion from goblet cells and increasing ciliary beat frequency. Denufosol tetrasodium (INS37217) inhalation solution (denufosol) is a novel second generation, chemically stable, selective P2Y2 receptor agonist under development by Inspire Pharmaceuticals, Inc. Denufosol may have the ability to restore or maintain mucociliary clearance in patients relatively early in the CF lung disease process, which may preserve lung function and lessen the inevitable repeat cycles of pulmonary bacterial colonization, pulmonary exacerbations, and chronic lung function decline. This multi-center, 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. At the completion of the 24-week placebo-controlled portion of this study, all patients will receive 60 mg denufosol three times daily for an additional 24 weeks in a safety extension period.