EFFICACY AND SAFETY OF DENUFOSOL TETRASODIUM (INS37217) INHALATION SOLUTION

这个子项目是众多研究子项目之一

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.