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：
9091268
负责人：
Boris Tabakoff
金额：
$ 100万
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 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9091268
关键词：
ADME Study Abstinence Accidents Acute Affect Age Alcohol consumption Alcohol dependence Alcohols Animals Autopsy Biological Biological Availability Blood Brain Canis familiaris Cardiovascular system Chemistry Chronic Clinical Clinical Trials Consumption Cyclic GMP Cytochrome P450 Data Development Dose Drug Formulations Drug Kinetics Enzymes Equilibrium Excretory function Female Funding Future GABA-A Receptor Grant Health Health Care Costs Heavy Drinking Hepatocyte Human In Vitro Incubated Individual Kilogram Knowledge Liver Microsomes Lung Macaca mulatta Maintenance Maximum Tolerated Dose Measures Medical Metabolic Metabolism Methods Modeling Monitor Monkeys Neurotransmitter Receptor Oral Oral Administration Organ Patients Permeability Pharmaceutical Preparations Pharmacotherapy Phase Plasma Plasma Proteins Population Positioning Attribute Primary Care Physician Procedures Production Productivity Protein Binding Quinolones Rattus Recombinants Recovery Relapse Reporting Residual state Safety Series Site Small Business Innovation Research Grant Societies Techniques Technology Testing Therapeutic Therapeutic Index Toxicokinetics Toxicology Treatment Failure United States Food and Drug Administration World Health Organization alcohol abuse therapy alcohol relapse alcohol use disorder arm base cost craving drinking drug distribution economic cost in vivo male meetings nonhuman primate novel phase 1 study phase 2 study prevent psychosocial public health relevance response scale up uptake

项目摘要

DESCRIPTION (provided by applicant): 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; the use of this formulation to repeat the relapse blocking effects of our compound in rats, and to extend our studies on reducing alcohol consumption with our compound to non- human primates. 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 monkeys). 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.

描述（由适用提供）：酒精使用障碍影响着18岁以上的美国人口的7.9％，每年的直接医疗费用，事故和生产力损失的年龄超过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结合使用。初级保健医师不等同于提供当前必要的治疗范围来治疗AUD，而治疗的适度作用会导致大量治疗疾病。我们已经在直接在一个主要的神经递质接收器之一上产生了一种新型分子，该分子因慢性过量饮酒而改变。我们还在依赖酒精的动物的两种不同的接力饮酒模型中证明了我们的药物可以减少或阻止这种缓解。我们对动物中化合物的安全性和代谢的初步研究使该化合物在人类临床试验中具有良好的治疗指数有信心。但是，在开始人类试验之前，我们需要我们的药物得到食品药品监督管理局的IND批准。为了实现这一里程碑，我们提出了一系列SBIR第一阶段的研究，这些研究包括开发口服公式，这对与人类的使用非常有吸引力；使用该配方重复大鼠中化合物的继电器阻塞效应，并扩展我们对将化合物减少饮酒量的研究扩展到非人类原发性的。在这些SBIR I期研究中，我们还将在新开发的配方中口服给药后建立药物的血液和大脑水平。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。 II期SBIR研究将完全专注于完成IND的所有FDA所需的所有研究，包括对体外代谢和代谢产物鉴定的完整研究，在两个物种（包括Rats and Monkeys）中的吸收，分布，代谢和排泄的体内研究，对安全性和毒理学（包括毒性学）的完整研究。这些研究将包括急性剂量研究以及长达六个月时间的急性剂量研究和慢性研究，因为我们预计人类的研究可能包括对药物的长期维持患者的长期维持。如果获得了IND设计，我们预计将通过本研究的手臂启动I期人体安全试验，以临床测量酒精依赖性受试者的渴望。如果这笔赠款是资助的，并且我们的药物达到了人类试验，我们预计会引入一种更有效，更高级使用的药物来治疗AUD。