WIRB - A PHASE 2, FIXED-SEQUENCE, OPEN-LABEL, SWITCH-OVER STUDY OF THE

WIRB - 第 2 阶段、固定序列、开放标签、切换研究

• 批准号: 8167309
• 负责人: Uta Lichter-Konecki
• 金额: $ 1.22万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-20 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167309
• 关键词: Ammonia; Blood; Blood specimen; Childhood; Computer Retrieval of Information on Scientific Projects Database; Diet; Dose; Enrollment; Funding; Grant; Institution; Measurement; Mole the mammal; Pharmaceutical Preparations; Phase; Phenylacetates; Phenylbutyrates; Protocols documentation; Research; Research Personnel; Resources; Safety; Source; Time; United States National Institutes of Health; Visit; design; open label

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 fixed-sequence, open-label, Switch Over study of HPN-100 with a long-term (12- month) Safety Extension part designed to assess the safety of HPN-100 in pediatric subjects and to prospectively assess the ability of HPN-100 to control blood ammonia as compared with NaPBA. Subjects will receive NaPBA three times daily (TID) with meals during the first week and the same PBA mole-equivalent dose of HPN-100 during the second week. If there are safety concerns regarding a single-step transition from NaPBA to HPN-100, at the investigator¿¿"s discretion, the transition may occur in 2 steps such that in the second week subjects may receive 50% of the PBA equivalent dose as NaPBA and 50% as HPN-100 before receiving 100% of the PBA equivalent dose as HPN-100 in the third week. Serial blood samples will be collected for PK and blood ammonia assessments after each drug has reached steady state, which is achieved approximately 4 days after initiation of 100% NaPBA or HPN-100 treatment. Subjects who complete the Switch Over part of the study will be offered the opportunity to continue in the study by entering the Safety Extension part of the study to continue receiving open-label HPN-100 for up to 12 months. Subjects who exit the protocol after enrollment but prior to completion of the study will have all the safety assessments, including safety labs and a single blood sample drawn for measurement of phenylbutyrate (PBA), the active metabolite phenylacetate (PAA), and the terminal metabolite phenylacetylglutamine (PAGN). The time of day at which the blood sample is drawn will be recorded as well as the time since the last dose of medication was taken. Subjects will follow a stable diet throughout the study as prescribed by the investigator and dietary compliance will be recorded at each study visit for both the Switch Over part and Safety Extension part of the study.

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。 这是一项 HPN-100 的固定序列、开放标签、转换研究，具有长期（12- 月）安全扩展部分旨在评估 HPN-100 在儿科受试者中的安全性 并前瞻性评估 HPN-100 控制血氨的能力 与NaPBA。 受试者将在第一周内每天随餐接受 3 次 NaPBA (TID)， 第二周内给予相同 PBA 摩尔当量剂量的 HPN-100。如果有安全的话 研究人员对从 NaPBA 到 HPN-100 的一步过渡的担忧 酌情决定，过渡可以分两步进行，以便在第二周受试者可以 在接受之前接受 PBA 等效剂量的 50% 作为 NaPBA 和 50% 作为 HPN-100 第三周，100% PBA 等效剂量为 HPN-100。系列血样将 每种药物达到稳定状态后收集用于 PK 和血氨评估， 这是在开始使用 100% NaPBA 或 HPN-100 后约 4 天实现的 治疗。 完成研究转换部分的受试者将有机会 通过进入研究的安全扩展部分来继续研究 接受开放标签 HPN-100 长达 12 个月。 在入组后但在研究完成之前退出方案的受试者将 所有安全评估，包括安全实验室和抽取的单一血液样本 苯丁酸 (PBA)、活性代谢物苯乙酸 (PAA) 和 末端代谢物苯乙酰谷氨酰胺（PAGN）。一天中抽血的时间 将记录抽取的样本以及自上次服药以来的时间 采取。 受试者将按照研究者的规定在整个研究过程中遵循稳定的饮食， 将在每次研究访视时记录转换部分和 安全扩展研究的一部分。