Nezavist a Novel Molecule for Treatment of Alcohol Use Disorder

Nezavist 是一种治疗酒精使用障碍的新型分子

• 批准号: 9762601
• 负责人: Boris Tabakoff
• 金额: $ 91.87万
• 依托单位: LOHOCLA RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762601
• 关键词: Accidents; Acute; Affect; Age; Alcohol consumption; Alcohol dependence; Alcohols; Animals; Applications Grants; Blood; Brain; Canis familiaris; Chronic; Clinical; Clinical Trials; Consumption; Cyclic GMP; Development; Dose; Excretory function; Formulation; Funding; Future; Grant; Health; Health Care Costs; Heavy Drinking; Human; In Vitro; Individual; Maintenance; Measures; Medical Care Costs; Metabolism; Modeling; Neurotransmitter Receptor; Oral; Oral Administration; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Population; Primary Care Physician; Production; Productivity; Rattus; Relapse; Reporting; Safety; Series; Small Business Innovation Research Grant; Societies; Testing; Therapeutic Index; Toxicokinetics; Toxicology; Treatment Failure; United States Food and Drug Administration; World Health Organization; absorption; alcohol abuse therapy; alcohol use disorder; arm; cost; craving; economic cost; in vivo; novel; phase 1 study; phase 2 study; prevent; psychosocial; scale up

Abstract from original grant application Alcohol Use Disorder affects 7.9% of the U.S. population ages 18 and older and costs society over $223 billion per year in direct medical costs, accidents and lost productivity. Current pharmacotherapy is only modestly effective and has to be used in conjunction with psychosocial treatment. Primary care physicians are ill equipped to provide the currently necessary range of therapy for treating AUD and the modest effects of therapy generate a significant number of treatment failures. We have generated a novel molecule with action directly at one of the major neurotransmitter receptors altered by chronic excessive consumption of alcohol. We have also demonstrated in two different models of relapse drinking by alcohol dependent animals that our medication can reduce or prevent such relapse. Our preliminary studies on the safety and metabolism of our compound in animals provide confidence that the compound will have a good therapeutic index in human clinical trials. Prior to embarking on the trials in humans we, however, need for our drug to be approved for an IND by the Food and Drug Administration. To be able to accomplish this milestone we are proposing a series of SBIR Phase I, IND enabling studies, which include the development of an oral formulation which will be attractive for use with humans. In these SBIR Phase I studies we will also establish the blood and brain levels of our drug after oral administration in the newly developed formulation. In the SBIR Phase II studies we will produce our drug under cGMP conditions and scale up production to meet future clinical trials. The Phase II SBIR studies will be fully focused on completing all of the FDA required studies for the IND, including complete studies of in vitro metabolism and metabolite identification, in vivo studies of Absorption, Distribution, Metabolism, and Excretion, complete studies on safety and toxicology (including toxicokinetics) in two species (rats and dogs). These studies will include escalating acute dose studies and sub-chronic and chronic studies of up to six months duration because we anticipate that human studies may include long term maintenance of patients on our medication. If an IND designation is obtained we anticipate launching a Phase I human safety trial with an arm of this study aimed at a clinical measure of craving in alcohol-dependent subjects. If this grant is funded and our medication reaches human trials we anticipate introducing a more efficacious and much more highly utilized medication to treat AUD.

原始赠款申请摘要 酒精使用障碍影响7.9%的美国18岁及以上人口， 社会每年直接医疗费用、事故和生产力损失超过2230亿美元。 目前的药物治疗效果有限，必须与 心理社会治疗初级保健医生没有能力提供目前的 治疗AUD的必要治疗范围和适度的治疗效果产生了 大量的治疗失败。我们已经产生了一种新的分子， 直接作用于一种被慢性过量 酒精消费。 我们还在两种不同的酒精复吸模型中证明了 依赖动物，我们的药物可以减少或防止这种复发。我们 对我们的化合物在动物中的安全性和代谢的初步研究提供了 相信该化合物将在人体临床试验中具有良好的治疗指数。 然而，在进行人体试验之前，我们需要我们的药物获得批准 申请食品和药物管理局的IND能够完成这个里程碑 我们提出了一系列SBIR I期IND启动研究，其中包括 开发一种对人类使用有吸引力的口服制剂。在这些 SBIR I期研究还将确定口服后药物的血液和大脑水平 在新开发的制剂中施用。在SBIR II期研究中，我们将 在cGMP条件下生产我们的药物，并扩大生产规模，以满足未来的临床需求 审判II期SBIR研究将完全专注于完成FDA要求的所有 IND研究，包括体外代谢和代谢产物的完整研究 鉴别，吸收、分布、代谢和排泄的体内研究， 完成对两个物种（大鼠和 狗）。这些研究将包括急性剂量递增研究和亚慢性和 长达六个月的慢性研究，因为我们预计人体研究可能 包括长期维持病人用药。如果IND名称是 我们预计将启动一项I期人体安全性试验， 旨在临床测量酒精依赖受试者的渴望。如果这笔资金 我们的药物进入人体试验，我们预计将引入一种更有效的， 治疗AUD的药物使用率更高。