(INS37217) INHALATION SOLUTION IN PATIENTS WITH CYSTIC FIBROSIS LUNG DISEASE

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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. The purpose of this study is to investigate the safety and effectiveness of two dose strengths of INS37217 compared to placebo. Placebo is a sterile saline (salt water) solution. The study drug (INS37217 or placebo) will be administered via a nebulizer three times per day for up to 28 days to patients with Cystic Fibrosis (CF) lung disease. It is hoped that this study will help select the appropriate dose for further studies of INS37217 in cystic fibrosis patients. Research to date shows promise that INS37217 Inhalation Solution can inhibit Na+ absorption, restore chloride ion conductance, rehydrate the airway surface, and produce dose-related increases in mucociliary clearance. While high doses can greatly enhance sputum expectoration in patients with CF lung disease, lower doses that normalize airway surface liquid and enhance mucociliary and cough clearance may be more appropriate for long-term therapy. The potential benefits of enhanced mucus clearance will likely be improved lung function, improved symptoms and possibly even lower infection and exacerbation rates long-term. Because of the short half-life of INS37217 (approximately 3 hrs in airway epithelial cells in vitro; Yerxa, 2002), three times daily (TID) dosing is being utilized to maximize the potential for restoring the normal conductance in the airways. Based on careful review of the results of the three earlier clinical trials, doses of INS37217 Inhalation Solution (20 mg and 60 mg administered via the PARI LC STAR¿ nebulizer and the PARI PRONEB¿ Turbo compressor) were selected for testing in this study. All patients will be exposed to TID doses of INS37217 or placebo (0.9% w/v solution of sterile sodium chloride) for 28 days.