A PHASE 2 STUDY OF PTC124 FOR CYSTIC FIBROSIS

PTC124 治疗囊性纤维化的 2 期研究

• 批准号: 7604667
• 负责人: Pamela L. Zeitlin
• 金额: $ 0.13万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604667
• 关键词: Age-Years; Canis familiaris; Clinical; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Development; Dose; Drug Kinetics; Drug usage; Funding; Genes; Grant; Institution; Label; Measures; Mediating; Nonsense Mutation; Nose; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Phase II Clinical Trials; Program Development; Protocols documentation; Range; Rattus; Research; Research Personnel; Resources; Safety; Site; Source; Time; Toxicology; Treatment Protocols; United States National Institutes of Health; base; cystic fibrosis patients; day; healthy volunteer; programs

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是一项IIa期、多中心、开放标签、剂量范围、疗效、安全性和 药代动力学（PK）研究18例无义突变介导的CF谁是？18岁本研究将作为整体开发项目的一部分进行，旨在获得PTC 124作为囊性纤维化跨膜传导调节因子（CFTR）基因无义突变所致CF患者治疗的监管批准。 无义突变介导的CF患者将在2个重复的28天周期（包括14天治疗和14天停药）中接受顺序递增剂量水平的PTC 124（在周期1中以4、4和8 mg/kg的剂量每天给药3次[TID]，在周期2中以10、10和20 mg/kg的剂量给药）。 TC 124治疗的总持续时间为28天，得到了大鼠和犬28天毒理学研究结果以及健康志愿者14天I期多次给药试验的安全性数据的支持。 本研究的主要目的是记录通过鼻跨上皮电位差（TEPD）的变化确定的药效学活性，给药方案可以安全给药。该方案将评估其他药理学活性指标，评价药物依从性，并评价PTC 124在CF患者中的安全性和PK。基于本研究中PTC 124的特征，将在注册指导的临床试验项目中继续进行用于CF患者的药物的临床开发。