METABOLIC IMAGING FOR DOSE EVALUATION IN CLINICAL TRIALS

用于临床试验剂量评估的代谢成像

• 批准号: 6073703
• 负责人: TERRY F BROWN
• 金额: $ 74.76万
• 依托单位: MIICRO, INC
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-15 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6073703
• 关键词: bioimaging /biomedical imaging; brain metabolism; clinical research; clinical trials; deoxyglucose; dosage; drug metabolism; drug receptors; drug screening /evaluation; fluoxetine; glucose metabolism; human subject; method development; pharmacokinetics; positron emission tomography; sertraline

The majority of CNS compounds dropped from clinical trials are abandoned due to an inability to demonstrate efficacy ill the target patient population These failures are often linked to the selection of in appropriate doses for investigation. This often necessitates the design and initiation of additional studies, resulting in significant delays and increased development costs. MIICRO's patented OMEI method uses FDG PET to determine the cerebral metabolic effects of drugs in humans. MIICRO uses its OMEI PET services to tell client pharmaceutical developers, in quantitative terms, whether a compound affects the brain, where it affects the brain, and how one drug compares to another. In Phase I of this project, we demonstrated that OMEI PET can characterize the dose-relate biological effects of a drug in the human brain and can establish the duration of tissue effects. We propose to extend our research and to develop a unique new service, the Optimum Dose Evaluation (ODE). When applied in early clinical tria1s, the ODE will help select appropriate dose ranges for subsequent clinical' trials. The ODE will thereby optimize the design of definitive-clinical trials, thus limiting the associated risk of failure and avoiding the expense of unnecessary trial arms. PROPOSED COMMERCIAL APPLICATION: Despite the fact that the development of CNS drugs is the largest and fastest-growing segment for pharmaceutical innovation and development, CNS drugs take longer, cost more, and are plagued with more failed trials than non-CNS drugs in development. A quantitative, cost-effective, new tool for evaluating drug doses will have a significant effect on the time and cost of CNS drug development, and will help avert failed trials due to inadequate data or poor study design.

由于无法证明对目标患者群体的疗效，大多数从临床试验中退出的中枢神经系统化合物都被放弃。这些失败通常与选择适当的剂量进行研究有关。这通常需要设计和启动额外的研究，从而导致严重的延误和开发成本的增加。 MIICRO 的专利 OMEI 方法使用 FDG PET 来确定药物对人体脑代谢的影响。 MIICRO 利用其 OMEI PET 服务，以定量的方式告诉客户药物开发人员，一种化合物是否影响大脑、影响大脑的部位以及一种药物与另一种药物的比较。 在该项目的第一阶段，我们证明OMEI PET可以表征药物在人脑中的剂量相关生物效应，并可以确定组织效应的持续时间。我们建议扩展我们的研究并开发一项独特的新服务，即最佳剂量评估（ODE）。当应用于早期临床试验时，ODE 将有助于为后续临床试验选择合适的剂量范围。因此，ODE 将优化最终临床试验的设计，从而限制相关的失败风险并避免不必要的试验组的费用。拟议的商业应用：尽管中枢神经系统药物的开发是药物创新和开发中规模最大且增长最快的部分，但与正在开发的非中枢神经系统药物相比，中枢神经系统药物需要更长的时间，成本更高，并且失败的试验更多。一种定量的、具有成本效益的评估药物剂量的新工具将对中枢神经系统药物开发的时间和成本产生重大影响，并将有助于避免由于数据不足或研究设计不良而导致试验失败。