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U 54中心将使用从大脑到床边的转化研究作为药物开发的工具， 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 决定进行II-III期临床试验，这些药物显示出对可卡因使用障碍的承诺。的 这项研究的总体目标是建立一个中心，可以提供重要的临床前和早期I期 向NIDA和制药行业合作伙伴提供治疗可卡因使用障碍的新型化合物的临床数据。 与中心主题相关的目标将通过两个核心和三个项目来实现： 行政核心（F。Gerard Moeller PI）作为其他项目的一般资源， 教育核心，包括监督财政和合规事项，并将监督与 包括NIDA和制药行业在内的外部实体。教育核心（William L.杜威PI） 将专注于培训翻译研究人员为药物开发成瘾横跨两个 机构职能体系项目1（F. Gerard Moeller PI）是一项I期人类药物相互作用研究， 同时给予可卡因与新化合物的效果，以及新化合物对 非寻求治疗的CocUD受试者对可卡因和可卡因自我给药的主观反应。 待研究的化合物将是S-HTac受体激动剂氯卡色林，随后是5-HT 2A受体 拮抗剂匹莫范色林基于项目3的结果。项目2（Joel L.斯坦伯格PI）是一个人类 神经影像学研究，以确定新化合物（氯卡色林，随后 pimavanserin）对戒断CocUD受试者在线索反应性任务期间的脑功能的影响，以提供进一步的 关于具体剂量的信息和关于II期临床试验通过/不通过决定的进一步证据， 药物作为加强预防复发的工具。项目3（凯瑟琳C。Cunningham PI）是临床前 检查新化合物（匹莫范色林和匹莫范色林加氯卡色林）对自我给药的影响的研究 并提示反应性，以填补CocUD潜在化合物缺乏的关键信息 并将为支持或反驳I期人体研究提供重要信息。