Medication Discovery Texas, Inc — Department of Health and Human Services STTR Phase I: NIAAA

Description

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 HT norepinephrine NE and dopamine DA Two triple uptake inhibitors DOV andamp amitifadine DOV have been shown to reduce alcohol self administration in rodents In a pilot study we showed that a newly developed triple reuptake inhibitor SKL reduced alcohol intake in rodents as well We now propose to evaluate SKL as a new treatment for alcohol dependence Phase I Specific Aim To conduct a human laboratory safety evaluation n of SKL and 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 when combined with an intoxicating dose of alcohol Milestone we will identify a dose of SKL that when combined with alcohol does not cause unacceptable toxicity defined as more than one SAE at the lowest dose of SKL Phase II Specific Aim To conduct a double blind randomized placebo controlled outpatient clinical trial of SKL as a treatment for alcohol dependence n The primary outcome measure will be proportion of self reported heavy drinking days e drinks day for males and e drinks day for females over the course of the study imputing dropouts as baseline rate a standard outcome in clinical trials for alcohol dependence PUBLIC HEALTH RELEVANCE Triple uptake inhibitors reduce alcohol intake by rodents and are therefore promising as treatments for alcohol dependence We propose translational and clinical research to evaluate the new triple uptake inhibitor SKL as a treatment for alcohol dependence