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.

该 U54 中​​心将利用从大脑到临床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 数据将为通过/不通过提供信息 关于对可卡因使用障碍有希望的药物进行 II-III 期临床试验的决定。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 I 期研究的中心 向 NIDA 和制药行业合作伙伴提供有关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： 管理核心（F. Gerard Moeller PI）作为其他项目和 教育核心，包括监督财务和合规事务，并将监督与 外部实体，包括 NIDA 和制药行业。教育核心（威廉·L·杜威 PI） 将重点培训转化研究人员，以开发针对这两种疾病的成瘾药物 机构。项目 1（F. Gerard Moeller PI）是一项 I 期人类药物相互作用研究，检查安全性 可卡因与新化合物同时给药的研究，以及新化合物对 非治疗寻求 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，其次是 5-HT2A 受体 拮抗剂 pimavanserin 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（氯卡色林，然后是 pimavanserin）对戒断 CocUD 受试者提示反应性任务期间大脑功能的影响，以提供进一步的信息 有关具体剂量的信息以及 II 期临床试验中进行/不进行决策的进一步证据，使用 药物作为加强预防复发的工具。项目 3（Kathryn C. Cunningham PI）是一项临床前研究 研究检查新型化合物（pimavanserin 和 pimavanserin 加 lorcaserin）对自我给药的影响 并提示反应性以填补 CocUD 潜在化合物所缺乏的关键信息 并将提供重要信息来支持或反驳第一阶段人体研究。