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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 这是一个 2a 期、多中心、开放标签、剂量范围、功效、安全性和 对 18 名 18 岁以下无义突变介导的 CF 患者进行的药代动力学 (PK) 研究。这项研究将作为总体开发计划的一部分进行，旨在获得监管机构批准 PTC124 用于治疗囊性纤维化跨膜电导调节因子 (CFTR) 基因无义突变引起的 CF 患者。 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）中接受连续、递增剂量水平的 PTC124（第 1 周期中每天给予 3 次 [TID]，剂量为 4、4 和 8 mg/kg，第 2 周期中剂量为 10、10 和 20 mg/kg）。 TC124 治疗的总持续时间为 28 天，得到了大鼠和狗 28 天毒理学研究结果的支持，以及来自健康志愿者为期 14 天的 1 期多剂量试验的安全性数据。 本研究的主要目的是记录通过鼻跨上皮电位差 (TEPD) 的变化以及可安全给药的给药方案确定的药效活性。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 在 CF 患者中的安全性和 PK。根据本研究对 PTC124 的表征，该药物用于 CF 患者的临床开发将在注册导向的临床试验计划中继续进行。