(INS37217) INHALATION SOLUTION IN PATIENTS WITH CYSTIC FIBROSIS 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。本研究旨在研究两种剂量规格INS 37217与安慰剂相比的安全性和有效性。安慰剂是一种无菌生理盐水溶液。囊性纤维化（CF）肺病患者将通过雾化器接受研究药物（INS 37217或安慰剂）给药，每日3次，持续28天。希望这项研究将有助于选择适当的剂量，用于在囊性纤维化患者中进行INS 37217的进一步研究。迄今为止的研究表明，INS 37217吸入溶液有望抑制Na+吸收，恢复氯离子电导，使气道表面再水化，并使粘膜纤毛清除率呈剂量相关性增加。虽然高剂量可以大大增强CF肺病患者的咳痰，但使气道表面液体正常化并增强粘膜纤毛和咳嗽清除的较低剂量可能更适合长期治疗。增强粘液清除的潜在益处可能是改善肺功能，改善症状，甚至可能长期降低感染和加重率。由于INS 37217的半衰期较短（体外气道上皮细胞中约3小时; Yerxa，2002），因此采用每日三次（TID）给药，以最大限度地恢复气道正常传导的潜力。 根据对三项早期临床试验结果的仔细审查，选择INS 37217吸入溶液（20 mg和60 mg，通过PARI LC星星雾化器和PARI PRONEB Turbo压缩机给药）用于本研究的试验。所有患者将暴露于TID剂量的INS 37217或安慰剂（0.9% w/v无菌氯化钠溶液）28天。

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.