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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。本研究的目的是研究INS37217两种剂量强度的安全性和有效性，并与安慰剂进行比较。安慰剂是一种无菌盐水溶液。研究药物(INS37217或安慰剂)将通过雾化吸入，每天三次，最多28天，用于囊性纤维化(CF)肺部疾病患者。希望这项研究能为INS37217在囊性纤维化患者中的进一步研究选择合适的剂量。到目前为止的研究表明，INS37217吸入液可以抑制Na+的吸收，恢复氯离子电导，恢复呼吸道表面的水化，并产生与剂量相关的粘液纤毛清除增加。虽然高剂量可显著增强CF肺部疾病患者的咳痰，但低剂量可使呼吸道表面液体正常化，并增强粘液纤毛和咳嗽清除，可能更适合长期治疗。增强粘液清除的潜在好处可能是改善肺功能，改善症状，甚至可能降低长期感染和恶化率。由于INS37217的半衰期很短(在体外呼吸道上皮细胞中约为3小时；Yerxa，2002)，每天三次(TID)剂量被用于最大限度地恢复呼吸道正常电导的潜力。在仔细回顾早期三个临床试验结果的基础上，选择INS37217雾化溶液剂量(通过Pari LC STAR雾化器和Pari ProNeb涡轮压缩机分别给药20 mg和60 mg)进行试验。所有患者都将暴露在INS37217或安慰剂(0.9%无菌氯化钠溶液)的TID剂量下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.