Preclinical Development of SCP-123 for Neuropathic Pain

SCP-123治疗神经性疼痛的临床前开发

• 批准号: 7560985
• 负责人: Kenneth W Narducy
• 金额: $ 45.46万
• 依托单位: ST. CHARLES PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7560985
• 关键词: Acetaminophen; Acute; Adverse effects; Affect; Alanine Transaminase; American; Amitriptyline; Analgesics; Animal Model; Animals; Anticonvulsants; Antidepressive Agents; Applications Grants; Carboxylic Acids; Chronic; Chung model; Clinical; Clinical Research; Clinical Trials; Codeine; Collaborations; Constriction procedure; Controlled Clinical Trials; Country; Data Analyses; Development; Dose; Drug Formulations; Drug Kinetics; Drug Packaging; Evaluation; Event; Funding; GPT gene; Glutathione; Grant; Health; Health Sciences; Hepatotoxicity; Histology; Human; Injury; Intravenous; Kidney; Lead; Lethal Dose 50; Life; Ligation; Liver; Measures; Mechanics; Methods; Modeling; Morphine; Mus; Nerve; Neuropathy; Nicotinamide adenine dinucleotide; Non-Steroidal Anti-Inflammatory Agents; Opiates; Oral; Pain; Pamphlets; Parents; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Placebo Effect; Positioning Attribute; Property; Protocols documentation; Publishing; Purpose; Radiolabeled; Rattus; Reporting; Research; Research Contracts; Research Design; Research Personnel; Research Project Grants; Resistance; Rodent Model; Rotarod Performance Test; Safety; Series; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solid; Solutions; Spinal nerve structure; Syndrome; Testing; Therapeutic; Thermal Hyperalgesias; Toxic effect; Transaminases; Translational Research; United States Food and Drug Administration; Water; Work; Writing; abstracting; allodynia; analog; base; chronic constriction injury; drug development; drug discovery; gabapentin; gastrointestinal; interest; man; motor deficit; painful neuropathy; pre-clinical; preclinical study; radiotracer; research study; response; sciatic nerve; trend; water solubility

Project Summary / Abstract Chronically, medically resistant pain is one of the most significant health problems in our country and affects more than 50 million Americans. Neuropathic pain syndromes are for the most part resistant to traditional analgesic treatments with NSAIDs, acetaminophen, or opiate medications (eg, morphine, codeine). Furthermore, most therapeutics currently used to treat neuropathic pain, including some antidepressants (eg, amitriptyline) and anticonvulsants (eg, gabapentin), were not specifically developed for that purpose, and show efficacy in only a fraction of the patients. We have been exploring a series of new and proprietary acetaminophen analogs, in which the lead compound (SCP-1) and it¿s active metabolite (SCP-123) show a favorable safety profile and are active in rodent models of neuropathic pain. In the first year under this Phase II SBIR translational research project, we will evaluate both an oral solid and an intravenous (iv) solution of SCP-123 in three models of neuropathic pain and compare them to gabapentin. We will also evaluate the safety and pharmacokinetic profile of these two formulations. When these evaluations are complete, we will analyze the data and choose one of the formulations as a clinical candidate. In the second and third year of this grant we will conduct the preclinical studies (on the chosen formulation) that are necessary for an Investigative New Drug (IND) application to the FDA. At the end of the third year of this grant project, we will write and assemble the IND package and submit it to the FDA. If the FDA accepts the IND application, we will shortly thereafter begin the Phase I human clinical of SCP-123

项目总结/摘要 长期以来，医学抗性疼痛是我国最重要的健康问题之一， 超过五千万美国人。神经性疼痛综合征在很大程度上对传统的治疗方法有抵抗力。 使用NSAID、对乙酰氨基酚或阿片类药物（如吗啡、可待因）进行镇痛治疗。 此外，目前用于治疗神经性疼痛的大多数疗法，包括一些抗抑郁药（例如， 阿米替林）和抗惊厥药（如加巴喷丁），并不是专门为此目的开发的， 仅在一小部分患者中显示出疗效。我们一直在探索一系列新的和专有的 对乙酰氨基酚类似物，其中先导化合物（SCP-1）及其活性代谢物（SCP-123）显示出 有利的安全性特征，并且在神经性疼痛的啮齿动物模型中具有活性。本阶段第一年 II SBIR转化研究项目，我们将评估口服固体和静脉（iv）溶液， SCP-123在三种神经性疼痛模型中的作用，并将其与加巴喷丁进行比较。我们还将评估 和这两种制剂的药代动力学特征。当这些评估完成后，我们将分析 数据，并选择其中一种制剂作为临床候选制剂。在第二年和第三年， 我们将进行临床前研究（对选定的配方），这是必要的研究新的 向FDA提交IND申请。在这个赠款项目的第三年年底，我们将编写和 组装IND包装并提交给FDA。如果FDA接受IND申请，我们将很快 之后开始SCP-123的第一阶段人类临床