Medication Development Center for cocaine Use Disorder

可卡因使用障碍药物开发中心

• 批准号: 9113541
• 负责人: FREDERICK Gerard MOELLER
• 金额: $ 123.36万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 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/9113541
• 关键词: Agonist; Brain; Clinical; Clinical Data; Clinical Trials; Cocaine; Cocaine Users; Data; Development; Disease; Dose; Drug Industry; Drug Interactions; FDA approved; Goals; HTR2A gene; Health; Human; Individual; Institution; Intervention; National Institute of Drug Abuse; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Population; Research; Research Methodology; Research Personnel; Resources; Safety; Self Administration; Training; Translational Research; United States Substance Abuse and Mental Health Services Administration; addiction; aged; base; cocaine use; cue reactivity; disorder later incidence prevention; dosage; industry partner; neuroimaging; novel; pre-clinical; preclinical study; receptor; response; tool

This U54 Center will use translational research from brain to bedside as a tool for medication development in cocaine use disorder. Preclinical and early phase I clinical PK/PD data will provide information for go/no-go decisions on phase II-III clinical trials with medications that show promise for cocaine use disorder. The overall goal of this research is to create a center that can provide important preclinical and early phase I clinical data to NIDA and pharmaceutical industry partners on novel compounds for cocaine use disorder. The aims related to the theme of the center will be achieved through two cores and three projects: The Administrative Core (F. Gerard Moeller PI) serves as a general resource for the other Projects and the Educational Core, including oversight of fiscal and compliance matters, and will oversee interactions with outside entities including NIDA and the pharmaceutical industry. The Educational Core (William L. Dewey PI) will focus on training translational researchers for medication development for addictions across the two institutions. Project 1 (F. Gerard Moeller PI) is a Phase I human drug interaction study examining the safety of concurrent administration of cocaine with novel compounds, and the effects of the novel compounds on subjective response to cocaine and cocaine self-administration in non-treatment seeking CocUD subjects. The compounds to be studied will be the S-HTac receptor agonist lorcaserin followed by the 5-HT2A receptor antagonist pimavanserin based on results of Project 3. Project 2 (Joel L. Steinberg PI) is a human neuroimaging study to determine the dose-related effects of the novel compounds (lorcaserin followed by pimavanserin) on brain function during cue reactivity tasks in abstinent CocUD subjects to provide further information on specific dosages and further evidence for go/no-go decisions on phase II clinical trials using medications as a tool to enhance relapse prevention. Project 3 (Kathryn C. Cunningham PI) is a preclinical study examining the effects of novel compounds (pimavanserin and pimavanserin plus lorcaserin) on self-administration and cue reactivity to fill in key information that is lacking on potential compounds for CocUD and will provide important information to support or refute phase I human studies.

这个U54中心将使用从大脑到床边的转化研究作为用于开发药物开发的工具 可卡因使用障碍。临床前和早期I期临床PK/PD数据将为GO/No-Go提供信息 对II-III期临床试验的决策，对可卡因使用障碍有望有望。这 这项研究的总体目标是创建一个可以提供重要的临床前和早期第一阶段的中心 NIDA和制药行业合作伙伴的临床数据，涉及可卡因使用障碍的新型化合物。 与中心主题相关的目标将通过两个核心和三个项目实现： 行政核心（F. Gerard Moeller Pi）是其他项目的一般资源， 教育核心，包括对财政和合规性事项的监督，并将监督与 NIDA和制药行业在内的外部实体。教育核心（William L. Dewey Pi） 将着重于培训翻译研究人员为两者中的成瘾的药物开发 机构。项目1（F. Gerard Moeller Pi）是一项I期人类药物相互作用研究，检查了安全性 同时施用可卡因与新型化合物以及新颖化合物的作用 对可卡因和可卡因自我管理的主观反应在寻求coud受试者的非治疗中。 要研究的化合物将是S-HTAC受体激动剂Lorcaserin，然后是5-HT2A受体 基于项目3的结果。项目2（Joel L. Steinberg Pi）是人类 神经影像学研究以确定新型化合物的剂量相关作用 pimavanserin）关于戒除的cocud受试者的提示反应性任务期间的大脑功能，以提供进一步的 有关特定剂量的信息和进一步的证据，以了解使用II期临床试验的GO/NO-GO决策 药物作为增强预防复发的工具。项目3（Kathryn C. Cunningham Pi）是临床前 研究研究了新型化合物（Pimavanserin和pimavanserin Plus lorcaserin）对自我给药的影响 和提示反应性以填充对Cocud潜在化合物缺乏的关键信息 并将提供重要的信息来支持或反驳I期人类研究。