PHARMACOKINETICS OF 552-02 FOLLOWING 14 DAYS OF DOSING BY INHALATION IN PTS W/CF

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该临床研究是一项针对囊性纤维化患者的多位点、双盲、安慰剂对照的2期研究。本研究的主要目的是评估552-02（一种特异性上皮钠通道抑制剂）在囊性纤维化患者每日雾化给药14天后的安全性和耐受性。次要目的是评估囊性纤维化患者每日雾化给药14天后552-02的血浆药代动力学。多达40名囊性纤维化患者将参与这项研究。患者将随机接受1.3毫克剂量的552-02或安慰剂（0.12%氯化钠），比例为1:1。患者将自行服用药物或安慰剂，每天一次，持续14天。雾化说明可在研究参考手册中找到。过早停用药物的患者可能会被替换。将进行筛查访问（第28天至第1天，访问1）。符合入组标准的患者将随机接受552-02或安慰剂治疗，持续14天（第1天至第14天）。所有患者将在研究第1天（访问2）、第7天（访问3）和第14天（访问4）访问诊所。受试者还将在治疗的第3天或第4天进行实验室访问，以进行临床化学评估，以验证钾水平在第1天至第7天之间没有上升趋势。门诊就诊的程序和评估包括给药、安全性评估（体格检查、肺活量测定、脉搏血氧测定、生命体征、心电图、血液学、临床化学、血浆检查、尿液分析）和不良事件评估。此外，将在第14天对被分配到PK亚组的患者采集血液样本进行药代动力学分析。患者将在第1、7和14天在诊所接受研究药物或安慰剂。所有患者将在研究第2-6天和第8-13天接受自我治疗。将在第1天和第7天通过电话联系患者，以评估不良事件。在服用最后一剂552-02或安慰剂3天后，还将通过电话联系患者，以评估不良事件。如果服用552-02或安慰剂14天与剂量限制性毒性的发展有关，则对个别患者暂停治疗。表1列出了详细的时间和活动安排，其中包括按学习日列出的所有计划评估的完整清单。

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. This clinical study is a multiple site, double blind, placebo-controlled Phase 2 study in patients with cystic fibrosis. The primary objective of this study is to evaluate the safety and tolerability of 552-02, a specific inhibitor of the epithelial sodium channel, after daily aerosolized administration for fourteen days in patients with cystic fibrosis. The secondary objective is to evaluate the plasma pharmacokinetics of 552-02 after daily aerosolized administration for fourteen days in patients with cystic fibrosis. Up to 40 patients with cystic fibrosis will participate in the study. Patients will be randomized to receive either a 1.3 milligram dose of 552-02 or placebo (0.12 % sodium chloride) in a 1:1 ratio. Patients will self-administer drug or placebo once daily for fourteen days by a nebulizer via the mouth. Instructions for nebulization can be found in the Study Reference Manual. Patients who prematurely discontinue may be replaced. A screening visit will be performed (Day -28 to Day -1, Visit 1). Eligible patients who meet the criteria for enrollment will be randomized to receive 552-02 or placebo daily for fourteen days (Day 1 through Day 14). All patients will visit the clinic on study Day 1 (Visit 2), Day 7 (Visit 3) and Day 14 (Visit 4). Subjects will also have a lab only visit at Day 3 or Day 4 of treatment for clinical chemistry assessment to verify that the potassium levels are not trending upward between Day 1 and Day 7. Procedures and assessments at clinic visits include dose administration, safety assessments (physical examination, spirometry, pulse oximetry, vital signs, ECGs, hematology, clinical chemistry, plasma panel, urinalysis), and assessment for adverse events. In addition, blood samples for pharmacokinetic analysis will be taken on Day 14 for patients assigned to the PK subgroup. Patients will receive study drug or placebo in the clinic on Days 1, 7 and 14. All patients will be instructed to self-administer treatment on study Days 2-6 and Days 8-13. Patients will be contacted by telephone on Day 1 and Day 7 to assess for adverse events. Patients will also be contacted by telephone three days following administration of the last dose of 552-02 or placebo to assess for adverse events. Treatment will be suspended on an individual patient basis if administration of 552-02 or placebo for fourteen days is associated with the development of dose limiting toxicity. A detailed Schedule of Time and Events is presented in Table 1, which includes a complete listing of all scheduled assessments by study day.