Center for the Development of Novel Medications for Cocaine Dependence

可卡因依赖新药开发中心

• 批准号: 8846714
• 负责人: KYLE Matthew KAMPMAN
• 金额: $ 108.89万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8846714
• 关键词: Agonist; Baclofen; Biometry; Brain; Brain imaging; Characteristics; Clavulanic Acids; Clinical Trials; Cocaine; Cocaine Dependence; Data; Detection; Development; Disease; Dopamine; Education; GABA Agonists; Genetic; Heterogeneity; Human; Investments; Laboratories; Online Systems; Patients; Pharmaceutical Preparations; Pharmacogenetics; Research; Research Infrastructure; Research Project Grants; Resources; Safety; Site; Testing; addiction; cocaine use; data management; dosage; efficacy trial; improved; innovation; neurobehavioral; neuroimaging; novel; placebo controlled study; programs; response; safety study; screening; volunteer

DESCRIPTION (provided by applicant): This application is to establish a U54 Medication Development Center of Excellence (MDCE). The proposed MDCE will be integrated within the umbrella of the Penn/VA Center for Studies of Addiction (CSA) and benefits greatly from that integration, permitting access to infrastructure and resources not generally available outside of a large research center. The MDCE has priority access to important resources: 1) the Berrettini genetics lab 2) the Center biostatistician; 3) a web-based Data Management Unit; and, 4) state-of the-art Brain Imaging. Our theme is the identification and comprehensive screening of innovative medications for the treatment of Cocaine Use Disorder (CUD). Our MDCE proposes to emphasize novel medications such as BP1.4979, a dopamine D3 partial agonist, the GABA B agonist, long acting baclofen and clavulanic acid (CLAV). In addition, we will improve our ability to identify efficacious new medications by identifying characteristics of CUD patients that may increase their likelihood of responding positively to a particular medication and by streamlining the identification of medication responders in clinical trials. The Administrative Core will coordinate and integrate a Human Laboratory and Genetics Pilot Program, an Education Core, a Biostatistics and Data Management Core and three research projects. The Human Laboratory and Genetics Pilot Program will employ neurobehavioral tasks that may aid in the detection of medication responders early in treatment and will explore pharmacogenetic interactions that could explain and potentially capitalize on heterogeneity in medication response. The research projects are arranged to allow for novel medications to be studied from safety through preliminary efficacy. In Project 1, we will administer cocaine to volunteers while receiving either BPI .4979 or CLAV to test for potential toxic interactions with cocaine, providing safety and preliminary efficacy data for these compounds. Project 2 will provide neurobehavioral and neuroimaging data to determine whether medications selected for study effectively engage the appropriate brain targets at the dosages proposed for study. Project 3 proposes to evaluate promising novel compounds in 12-week, placebo-controlled trials. By providing comprehensive screening of candidate medications and sequentially testing them, as described, we expect to rapidly identify effective medications that justify investment in the next level of development, multi-site efficacy trials.

描述（由申请人提供）：本申请旨在建立 U54 药物开发卓越中心 (MDCE)。拟议的 MDCE 将整合到宾夕法尼亚州/退伍军人管理局成瘾研究中心 (CSA) 的范围内，并从这种整合中受益匪浅，允许访问一般在外部机构之外无法获得的基础设施和资源。 大型研究中心。 MDCE 可以优先获取重要资源：1) Berrettini 遗传学实验室 2) 中心生物统计学家； 3) 基于网络的数据管理单元； 4) 最先进的脑成像。我们的主题是识别和全面筛选用于治疗可卡因使用障碍 (CUD) 的创新药物。我们的 MDCE 建议重点关注新型药物，例如 BP1.4979、多巴胺 D3 部分激动剂、GABA B 激动剂、长效巴氯芬和克拉维酸 (CLAV)。此外，我们将通过识别 CUD 患者的特征来提高识别有效新药物的能力，这些特征可能会增加他们对特定药物产生积极反应的可能性，并简化临床试验中药物反应者的识别。行政核心将协调和整合人类实验室和遗传学试点计划、教育核心、生物统计和数据管理核心以及三个研究项目。人类实验室和遗传学试点计划将采用神经行为任务，有助于在治疗早期检测药物反应者，并将探索药物遗传学相互作用，以解释并可能利用药物反应的异质性。这些研究项目的安排是为了对新药物进行从安全性到初步疗效的研究。在项目 1 中，我们将在志愿者接受可卡因的同时服用可卡因 BPI .4979 或 CLAV 用于测试与可卡因的潜在毒性相互作用，为这些化合物提供安全性和初步功效数据。项目 2 将提供神经行为和神经影像数据，以确定为研究选择的药物是否能以建议研究的剂量有效地作用于适当的大脑目标。项目 3 提议在为期 12 周的安慰剂对照试验中评估有前景的新型化合物。如上所述，通过对候选药物进行全面筛选并按顺序进行测试，我们期望快速识别有效药物，证明投资下一阶段的开发、多中心疗效试验是合理的。