A new class of non-opioid analgesics for use in chronic pain management

用于慢性疼痛管理的新型非阿片类镇痛药

• 批准号: 8904491
• 负责人: KEVIN D BUNKER
• 金额: $ 124.29万
• 依托单位: KALYRA PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8904491
• 关键词: Acetaminophen; Acute; Acute Liver Failure; Acute Pain; Address; Adverse effects; Analgesics; Antidepressive Agents; Antiepileptic Agents; Canis familiaris; Cardiac; Cessation of life; Clinical; Clinical Trials; Coxibs; Data; Development; Dose; Drug Formulations; Drug Kinetics; Emergency department visit; Ensure; Enzyme Inhibition; Exhibits; Formalin; Goals; Half-Life; Hand; Hospitalization; Human; Imines; In Vitro; Lead; Legal patent; Literature; Liver; Liver Failure; Medical; Metabolism; Methods; Modeling; Mus; Narcotics; Non-Steroidal Anti-Inflammatory Agents; Overdose; Pain; Pain management; Pathology; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Plasma; Postoperative Pain; Property; Rattus; Recording of previous events; Risk; Rodent; Route; Safety; Scientist; Societies; Surgical incisions; Technology; Testing; Toxicology; addiction; analog; base; chronic pain; clinical toxicology; comparative efficacy; cost; disability payment; drug candidate; effective therapy; genotoxicity; improved; in vivo; liver injury; meetings; novel; p-Benzoquinones; para-benzoquinone; preference; productivity loss; public health relevance; screening; small molecule

 DESCRIPTION (provided by applicant): Acute and chronic pain imposes a tremendous burden on society, not only because of the associated human suffering, but also the cost of medical treatment, loss of productivity and disability payments, which has been estimated to be up to $650 billion per year in the USA alone. Current treatments for pain are hampered by limited efficacy and acute or long-term side effects. Acetaminophen is an important drug in the management of pain; however, overdose (which is quite common) can lead to liver damage, subsequent liver failure, and even death. A safe non-liver toxic drug, with equal or improved efficacy compared to acetaminophen, would be a ground breaking new product for the treatment of pain. Kalyra Pharmaceuticals has synthesized a number of structurally related acetaminophen analogs, utilizing our toolbox of proprietary bioisosteres, and discovered new highly potent analgesic compounds that do not form a toxic metabolite. With proof of concept in hand, further development of these analogues is the subject of this direct to Phase II proposal, via the Specific Aims outlined below: Phase II: Non-Clinical Development of a New Treatment for Pain Aim 1. Further Characterization of Efficacy and In Vivo Pharmacology Aim 2. ADMET, Additional Pharmacology and Preliminary Toxicology Aim 3. Pharmacokinetic Studies to Confirm Second Species Selection for Safety Aim 4. Non-Clinical Toxicology Studies in Support of Filing of an IND After completion of the IND-enabling studies outlined in this proposal, we anticipate the filing of an IND with the FDA to begin human clinical trials for the development of a novel, safe, effective and non-addictive new treatment for the management of pain.

 描述（由申请人提供）：急性和慢性疼痛给社会带来了巨大的负担，不仅因为相关的人类痛苦，而且还因为医疗费用、生产力损失和残疾赔偿金，据估计仅在美国每年就高达 6500 亿美元。目前的疼痛治疗方法因疗效有限和急性或长期副作用而受到阻碍。 对乙酰氨基酚是治疗疼痛的重要药物；然而，过量（这很常见）会导致肝损伤、随后的肝功能衰竭，甚至死亡。一种安全的非肝毒性药物，与对乙酰氨基酚相比具有相同或更好的功效，将是治疗疼痛的突破性新产品。 Kalyra Pharmaceuticals 利用我们专有的生物等排体工具箱合成了许多结构相关的对乙酰氨基酚类似物，并发现了不会形成有毒代谢物的新型高效镇痛化合物。有了概念验证，这些类似物的进一步开发是直接进入第二阶段提案的主题，具体目标如下： 第二阶段：疼痛新疗法的非临床开发 目标 1. 进一步表征功效和体内药理学目标 2. ADMET、其他药理学和初步毒理学目标 3. 药代动力学研究以确认安全性的第二个物种选择 目标 4.支持备案的非临床毒理学研究 完成本提案中概述的 IND 授权研究后，我们预计将向 FDA 提交 IND 申请，开始人体临床试验，开发一种新颖、安全、有效且不成瘾的疼痛治疗新疗法。