Medication Development Center for cocaine Use Disorder

 描述（由申请人提供）：该U 54中心将使用从大脑到床边的转化研究作为可卡因使用障碍药物开发的工具。临床前和早期I期临床PK/PD数据将为II-III期临床试验的进行/不进行决策提供信息，这些临床试验使用显示出对可卡因使用障碍有希望的药物。这项研究的总体目标是建立一个中心，为NIDA和制药行业合作伙伴提供重要的临床前和早期I期临床数据，用于治疗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来实现：行政核心（F。Gerard Moeller PI）担任其他项目和教育核心的一般资源，包括监督财务和合规事项，并将监督与外部实体（包括NIDA和制药行业）的互动。教育核心（William L.杜威PI）将专注于培训翻译研究人员在两个机构的药物开发成瘾。项目1（F. Gerard Moeller PI）是一项I期人类药物相互作用研究， 同时施用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受试者中对可卡因和可卡因自我施用的主观反应的影响。根据项目3的结果，待研究的化合物将是5-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。项目2（Joel L. Steinberg PI）是一项人类神经成像研究，以确定新型化合物（氯卡色林，随后是匹莫范色林）在戒断CocUD受试者的线索反应性任务期间对脑功能的剂量相关影响，以提供关于特定剂量的进一步信息和使用药物作为增强复发预防的工具的II期临床试验的进行/不进行决定的进一步证据。项目3（凯瑟琳C。Cunningham PI）是一项临床前研究，检查了新型化合物（匹莫范色林和匹莫范色林加氯卡色林）对自我给药和线索反应性的影响，以填补缺乏的关键信息。 CocUD的潜在化合物，并将提供重要的信息，以支持或反驳I期人体研究。

 DESCRIPTION (provided by applicant): 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 ll-lll 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 5-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.