A PHASE 2 STUDY OF PTC124 FOR CYSTIC FIBROSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一种2a期，多部位，开放标签，剂量范围，有效性，安全性和 18例18岁无义突变介导的CF患者的药代动力学研究.这项研究将作为总体开发计划的一部分进行，旨在获得监管部门的批准，将PTC124用于治疗囊性纤维化跨膜传导调节器(CFTR)基因无义突变引起的CF患者。 患有无义突变介导的CF的患者将在2个重复的28天周期中接受PTC124的连续、递增剂量水平的治疗(第1周期每天给药3次，剂量为4、4和8 mg/kg，第2周期为10、10和20 mg/kg)，共2个重复的28天周期，包括14天治疗和14天停药。 TC124治疗的总持续时间为28天，这得到了在大鼠和狗身上持续28天的毒理学研究结果以及来自健康志愿者14天第一阶段多剂量试验的安全性数据的支持。 这项研究的主要目的是记录由鼻腔跨上皮电势差(TEPD)的变化确定的药效学活性，给药方案可以安全地给药。该方案将评估其他药理活性指标，评估药物依从性，并评估PTC124的安全性和CF患者的PK。根据这项研究中PTC124的特点，该药物的临床开发将继续在注册指导的临床试验计划中进行，用于CF患者。

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 is a Phase 2a, multi-site, open-label, dose-ranging, efficacy, safety, and pharmacokinetic (PK) study in 18 patients with nonsense-mutation-mediated CF who are ?18 years of age. This study will be conducted as part of an overall development program aimed at obtaining regulatory approval of PTC124 as treatment for patients with CF resulting from a nonsense mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with nonsense-mutation-mediated CF will receive sequential, escalating dose levels ofPTC124 (given 3 times per day [TID] at doses of 4-, 4-, and 8-mg/kg in Cycle 1, and 10-, 10-, and 20-mg/kg in Cycle 2) in 2 repeated 28-day cycles comprising 14 days on therapy and 14 days off therapy. The total duration of TC124 treatment, 28 days, is supported by the results of toxicology studies of 28 days duration in rats and dogs, and safety data derived from the 14-day Phase 1 multiple-dose trial in healthy volunteers. The primary objective of this study is to document pharmacodynamic activity as determined by changes in the nasal transepithelial potential difference (TEPD) with a dosing regimen that can be safely administered. The protocol will assess other measures of pharmacological activity, evaluate drug compliance, and evaluate PTC124 safety and PK in CF patients. Based on thecharacterization of PTC124 from this study, clinical development of the drug for use in patients with CF will continue in a registration-directed clinical trials program.