DELTA F508 CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

DELTA F508 囊性纤维化跨膜电导调节器

• 批准号: 7378930
• 负责人: MICHAEL D. BOYLE
• 金额: $ 0.55万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378930
• 关键词: DELTA; F508; CYSTIC; FIBROSIS; TRANSMEMBRANE

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 I, open label, safety and dose finding study of advancing doses of orally administered curcuminoids in adult subjects with cystic fibrosis who are homozygous for ?F508 CFTR mutation. The primary objective of this study is to assess the safety of advancing doses of curcuminoids administered orally for fourteen consecutive days in adult subjects with cystic fibrosis (CF) who are homozygous for ?F508 CFTR. The secondary objectives of this study are: 1) to obtain pharmacokinetic data for oral curcuminoids in CF subjects, 2) to assess the efficacy of curcuminoids to alter ion transport across respiratory epithelia by measurement of nasal potential difference (NPD), and 3) to make a preliminary assessment of the potential efficacy of curcuminoids to alter ion transport across sweat duct epithelia by measurement of sweat chloride concentrations. The study is non-randomized and open label with no placebo control. It will consist of a single 14-day dosing cohort in which an initial dose level will be administered for 7 days, followed by a higher dose level administered for 7 days. Approximately 10 subjects will be enrolled in the cohort in order to achieve a total of 8 evaluable subjects. Two (2) sites will be involved in the study. Subjects will receive 1.5 grams of study drug three times per day (TID) (Dose Level 1) for 7 consecutive days, followed by 3 grams of study drug TID (Dose Level 2) for 7 consecutive days. The length of study participation for each subject will be approximately 34 days and consist of 5 study Visits defined as: Visit 1 (Screening, Day -14 to -10 where Day 1 is that day on which the subject will receive their first dose of study drug), Visit 2 (Baseline measurements and initiation of study drug, Day 1), Visit 3 (Initiation of higher dose, Day 8), Visit 4 (final dose of study drug, Day 15), and Visit 5 (Follow-up, Day 22). Study drug will first be administered at the initial dose level in the afternoon at Visit 2 (Day 1). The subject will take study drug at home on the evening of Day 1 and three times a day, morning, afternoon and evening, on Days 2 through 7. The final dose of study drug at the initial dose level will be administered on the morning of Visit 3 (Day 8). Study drug will be administered at the higher dose level in the afternoon at Visit 3 (Day 8). The subject will take study drug at the higher dose level at home on the evening of Day 8 and three times a day on Days 9 through 14. The final dose at the higher dose level will be administered in the morning at Visit 4 (Day 15). Subjects will be allowed the option of staying in the site GCRC overnight prior to Visits 3 and 4 to allow the Visit procedures to begin at an appropriate time on those mornings (@ 8am). The study will assess changes in safety parameters, and changes in Nasal Potential Difference (NPD) measurements between Visits at screening (Visit 1), Day 8 (Visit 3, after final dose at initial dose level) and Day 15 (Visit 4, after the final dose of study drug). A baseline sweat chloride measurement will be obtained at Visit 1 (screening), or at Visit 2 prior to dosing, or any day between Visits 1 and 2. A post-treatment sweat chloride measurement will be performed on Visit 4 following the final dose of study drug. A plasma collection will be obtained for baseline pharmacokinetic (PK) analysis at Visit 2 (Day 1) prior to the first dose of study drug. Sequential PK collections will be obtained following the first dose of study drug on Visit 2, following the last administration of study drug at the initial dose level on Visit 3 (Day 8), and following the last administration of study drug at the higher dose level on Visit 4 (Day 15).

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。这是一项 I 期、开放标签、安全性和剂量探索研究，目的是在 ?F508 CFTR 突变纯合的囊性纤维化成年受试者中增加口服姜黄素的剂量。本研究的主要目的是评估对于 ?F508 CFTR 纯合子的囊性纤维化 (CF) 成年受试者，连续十四天口服增加剂量姜黄素的安全性。本研究的次要目标是：1) 获得 CF 受试者中口服类姜黄素的药代动力学数据，2) 通过测量鼻电位差 (NPD) 评估类姜黄素改变呼吸道上皮离子转运的功效，3) 初步评估类姜黄素改变汗管上皮离子转运的潜在功效 通过测量汗液氯化物浓度。该研究是非随机、开放标签的，没有安慰剂对照。它将由一个为期 14 天的剂量组组成，其中初始剂量水平将施用 7 天，随后施用更高剂量水平，持续 7 天。大约 10 名受试者将被纳入该队列，以获得总共 8 名可评估受试者。该研究将涉及两 (2) 个地点。受试者将连续 7 天每天 3 次 (TID)（剂量水平 1）接受 1.5 克研究药物，然后连续 7 天接受 3 克研究药物 TID（剂量水平 2）。每个受试者参与研究的时间约为 34 天，包括 5 次研究访问，定义为：访问 1（筛选，第 -14 至 -10 天，其中第 1 天是受试者接受第一剂研究药物的那一天）、访问 2（基线测量和开始研究药物，第 1 天）、访问 3（开始更高剂量，第 8 天）、访问 4（研究药物的最终剂量，第 15 天）和访问 5 （后续，日 22）。研究药物将首先在第 2 次访视（第 1 天）下午以初始剂量水平给药。受试者将在第 1 天晚上在家服用研究药物，并在第 2 天至第 7 天每天早上、下午和晚上服用 3 次。初始剂量水平的研究药物的最终剂量将在第 3 天（第 8 天）的早上服用。研究药物将在第 3 次访视下午（第 8 天）以较高剂量水平给药。受试者将在第 8 天晚上在家服用较高剂量水平的研究药物，并在第 9 天至第 14 天每天服用 3 次。较高剂量水平的最终剂量将在第 4 次访视的早上（第 15 天）服用。受试者可以选择在第 3 次和第 4 次访问之前在 GCRC 现场过夜，以便访问程序在这些早晨的适当时间（@ 上午 8 点）开始。该研究将评估筛选时访视（访视 1）、第 8 天（访视 3，初始剂量水平最终剂量后）和第 15 天（访视 4，最终剂量研究药物后）之间安全参数的变化以及鼻电位差 (NPD) 测量值的变化。基线汗液氯化物测量将在第 1 次访视（筛选）或给药前第 2 次访视或第 1 次访视和第 2 次访视之间的任何一天进行。治疗后汗液氯化物测量将在研究药物最终剂量后的第 4 次访视时进行。在第一次给予研究药物之前的第 2 次访视（第 1 天）时将采集血浆用于基线药代动力学 (PK) 分析。连续 PK 收集将在第 2 次访视首次给药研究药物后、第 3 次访视（第 8 天）最后一次以初始剂量水平给药研究药物后以及第 4 次访视（第 15 天）最后一次以较高剂量水平给药研究药物后获得。