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

基本信息

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
项目类别：
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

项目摘要

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.

原始赠款申请中的摘要酒精使用障碍影响18岁及以上的美国人口的7.9％，成本社会每年的直接医疗费用，事故和生产力损失超过2230亿美元。当前的药物治疗仅适度有效，必须与社会心理治疗。初级保健医生不具备提供当前的治疗AUD的必要范围和治疗的适度作用会产生A 大量治疗失败。我们已经产生了一个新颖的分子直接在一个主要的神经递质受体之一中，慢性过度改变饮酒的消费。我们还在两种不同的饮酒模型中证明了我们的药物可以减少或防止这种复发的依赖动物。我们的关于我们化合物在动物中的安全性和代谢的初步研究提供在人类临床试验中，该化合物将具有良好的治疗指数的信心。但是，在开始进行人类试验之前，我们需要批准我们的药物食品药品监督管理局的IND。能够完成这个里程碑我们提出了一系列SBIR第一阶段，促进研究，其中包括开发口服配方，这将有吸引力与人类一起使用。在这些 SBIR I期研究我们还将在口服后建立药物的血液和大脑水平新开发的配方中的管理。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以满足未来的临床试验。第二阶段SBIR研究将完全专注于完成所需的所有FDA IND的研究，包括对体外代谢和代谢产物的完整研究鉴定，体内研究，分布，代谢和排泄，关于两个物种的安全性和毒理学（包括毒理学）的完整研究狗）。这些研究将包括急性剂量研究和亚基次数升级长达六个月的长期研究，因为我们预计人类研究可能会包括在我们的药物治疗中对患者的长期维护。如果指定为获得了我们预计将通过本研究的一臂之力启动I期人类安全试验针对酒精依赖受试者渴望的临床度量。如果这笔赠款是资助的我们的药物达到了人类试验，我们期望引入一个更有效和更有效的更高度使用的药物来治疗AUD。