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Triple Re-uptake Inhibitor, SKL 10406, as a New Treatment for Alcohol Dependence

三重再摄取抑制剂 SKL 10406，作为酒精依赖的新治疗方法

基本信息

批准号：
8834162
负责人：
Thomas Frederick Newton
金额：
$ 13.99万
依托单位：
MEDICATIONS DISCOVERY TEXAS, INC.
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 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8834162
关键词：
Adverse effects Adverse event Affect Alcohol consumption Alcohol dependence Alcohols Attenuated Biological Assay Characteristics Clinical Clinical Research Clinical Trials Cocaine DOV 216303 Data Desipramine Disulfiram Dopamine Dose Dose-Limiting Double-Blind Method Dropout Evaluation FDA approved Female Fluoxetine Headache Heavy Drinking Human Laboratories Maximum Tolerated Dose Mediating Modeling Naltrexone Nausea Norepinephrine Outcome Outcome Measure Outpatients Participant Pathogenesis Pathway interactions Patient Self-Report Patients Pharmaceutical Preparations Phase Phase II Clinical Trials Physicians Pilot Projects Placebo Control Placebos Play Population Prazosin Publishing Randomized Rattus Rewards Rodent Role Safety Selective Serotonin Reuptake Inhibitor Self Administration Serotonin Signal Transduction Sucrose Time Toxic effect Translational Research acamprosate alcohol effect alcohol reinforcement alcohol use disorder binge drinking blind drinking drug discrimination effective therapy enantiomer experience healthy volunteer inhibitor/antagonist male monoamine nalmefene neurotransmission noradrenergic pre-clinical presynaptic neurons primary outcome public health relevance receptor reduced alcohol use response reuptake topiramate uptake

项目摘要

DESCRIPTION (provided by applicant): Three medications are approved by the FDA as treatments for alcohol dependence: disulfiram, acamprosate and naltrexone, but these are seldom prescribed due to poor efficacy or side effects. Another, topiramate, is effective for reducing alcohol use but it causes a range of side effects that limit its tolerability. Another clas of potentially effective treatments includes triple uptake inhibitors. Triple uptake inhibitors enhance neural signaling that is mediated by serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Two triple uptake inhibitors (DOV 102,677 & amitifadine/DOV 21,947) have been shown to reduce alcohol self-administration in rodents. In a pilot study we showed that a newly developed triple reuptake inhibitor, SKL 10406, reduced alcohol intake in rodents as well. We now propose to evaluate SKL 10406 as a new treatment for alcohol dependence. Phase I Specific Aim: To conduct a human laboratory safety evaluation (n=20) of SKL 10406 (25, 50, and 75 mg PO BID) alone and combined with alcohol in alcohol-experienced healthy volunteers. Dose escalation and stopping rules are in place. This study will characterize the side effects, safety profile, and maximum tolerated dose of SKL 10406 when combined with an intoxicating dose of alcohol. Milestone: we will identify a dose of SKL 10406 that when combined with alcohol does not cause unacceptable toxicity, defined as more than one SAE at the lowest dose of SKL 10406. Phase II Specific Aim: To conduct a double-blind, randomized placebo-controlled outpatient clinical trial of SKL 10406 as a treatment for alcohol dependence (n=72). The primary outcome measure will be proportion of self-reported heavy drinking days (e5 drinks/day for males and e4 drinks/day for females) over the course of the study (imputing dropouts as baseline rate), a standard outcome in clinical trials for alcohol dependence.