Medication Development Center for cocaine Use Disorder

 描述(由申请人提供)：这个U54中心将使用从大脑到床边的翻译研究作为治疗可卡因使用障碍的药物开发的工具。临床前和早期I期临床PK/PD数据将为11期临床试验的进行/不进行决策提供信息，这些试验使用的药物显示可卡因使用障碍的前景。这项研究的总体目标是创建一个中心，向NIDA和制药业合作伙伴提供治疗可卡因使用障碍的新化合物的重要临床前和早期I期临床数据。与中心主题有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)作为其他项目和教育核心的一般资源，包括监督财政和合规事项，并将监督与包括NIDA和制药业在内的外部实体的互动。教育核心(William L.Dewey Pi)将专注于为两个机构的成瘾药物开发培训翻译研究人员。项目1(F.Gerard Moeller Pi)是一项第一阶段的人类药物相互作用研究，旨在检查安全性 与新化合物同时使用可卡因的情况，以及新化合物对非寻求治疗的慢性阻塞性肺病患者对可卡因和可卡因自我给药的主观反应的影响。根据项目3的结果，将要研究的化合物将是5-HTAC受体激动剂氯卡色林和5-HT2A受体拮抗剂匹马福林。项目2(Joel L.Steinberg PI)是一项人类神经成像研究，旨在确定在戒断CocUD受试者的线索反应任务中，新型化合物(氯卡色林和匹马色林)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，以及使用药物作为工具加强复发预防的II期临床试验中做出GO/NO-GO决定的进一步证据。项目3(Kathryn C.Cunningham Pi)是一项临床前研究，旨在研究新化合物(吡喃丝氨酸和吡喃丝氨酸加氯酪蛋白)对自我给药和线索反应性的影响，以填补缺乏的关键信息 潜在的COUD化合物，并将为支持或驳斥第一阶段人类研究提供重要信息。

 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.