Center for the Development of Novel Medications for Cocaine Dependence

可卡因依赖新药开发中心

• 批准号: 8925041
• 负责人: KYLE Matthew KAMPMAN
• 金额: $ 102.03万
• 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/8925041
• 关键词: Address; 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; Medical; Online Systems; Patients; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Population; Public Health; Research; Research Infrastructure; Research Project Grants; Resources; Safety; Site; Testing; addiction; cocaine use; data management; dosage; economic cost; 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U 54卓越药物开发中心（MDCE）。拟议的MDCE将被整合到宾夕法尼亚州/弗吉尼亚州成瘾研究中心（CSA）的保护伞内，并从这种整合中受益匪浅，允许访问基础设施和资源，而这些基础设施和资源通常是在一个 大型研究中心。MDCE优先获得重要资源：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;以及，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药物使用障碍（CUD）的创新药物。我们的MDCE建议强调新的药物，如BP 1.4979，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，并通过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，这可能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，可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允许从安全性到初步疗效对新药进行研究。在项目1中，我们将向志愿者注射可卡因，同时接受 BPI .4979或CLAV测试与可卡因的潜在毒性相互作用，提供这些化合物的安全性和初步疗效数据。项目2将提供神经行为和神经影像学数据，以确定选择用于研究的药物是否在研究的建议剂量下有效地参与适当的大脑靶点。项目3建议在为期12周的安慰剂对照试验中评估有前途的新化合物。通过提供候选药物的全面筛选和顺序测试，如所述，我们希望快速识别有效的药物，证明投资于下一个发展水平，多站点疗效试验。