A Novel Compound for Alcoholism Treatment

Exclusion Criteria

• •Interest in receiving treatment for heavy drinking.
• •Current DSM-IV diagnosis (based on SCID) of substance dependence (other than alcohol and/or nicotine); a negative urine drug screen will also be required.
• •DSM-IV Axis I criteria for a lifetime diagnosis of schizophrenia, bipolar disorder, or other psychoses;
• •Active illness within the past 6 months of the screening visit that meet the DSM-IV criteria for a diagnosis of major depressive disorder or anxiety disorder; subjects with a history of attempted suicide will be excluded;
• •Clinically significant medical abnormalities (e.g., unstable hypertension, clinically significant EKG abnormalities, Creatinine greater than or equal to 2 mg/dL, liver cirrhosis, AST or ALT \> 3x the upper normal limit, hemoglobin \<10.5 g/dl);
• •Heart rate \>100 at screening on two separate measurements given potential of study medication to increase heart rate.
• •BMI less than or equal to 18.5 or anorexia given potential of the study medication to reduce appetite.
• •BMI greater than or equal to 35 kg/m\^2.
• •Exclusionary Medications:
• •* Naltrexone, acamprosate, alcohol dehydrogenase inhibitors, topiramate, gabapentin, ondansetron, benzodiazepines, beta-blockers, H2-blockers, and alpha-1 blockers, baclofen, and barbiturates as well as hormone replacement therapy; medications and dietary/herbal supplements (like St. John's wort) that interact with Cytochrome P450 3A4. All of the medications in the previous sentence will not be allowed if they have been taken within 2 weeks of study medication administration.
• •* PF-05190457 is a substrate for P-glycoproteins (P-gp or encoded by ABCB1 gene) based on information from in vitro or animal models. Patients that are required to take the following inhibitors and inducers of P-gp are excluded unless the subject stops taking these agents for 2 weeks for P-gp inhibitors or 6 weeks for P-gp inducers before study medication administration.
• •Inhibitors: Amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, verapamil
• •Inducers: Avasimibe, carbamazepine, phenytoin, rifampin, St John s wort, tipranavir/ritonavir \[From Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers, table 12, from http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#substrates\]
• •History of epilepsy or alcohol-related seizures;
• •patients who have diabetes and/or are treated with any drug with glucose lowering properties such as sulfonylurea, insulin, metformin, thiazolidinediones (TZD), Dipeptidyl peptidase-4(DPP4) inhibitors, or Glucagon-like peptide-1(GLP-1)agonists (due to the glucose-lowering properties of PF-05190457 observed in healthy volunteers);
• •History of alcohol-induced flushing reactions.
• •Clinically significant alcohol withdrawal symptoms, as assessed by a CIWA-Ar score \> 8 at screening.
• •Any other reason or clinical condition for which the PI or the MAI will consider unsafe for a possible participant to participate in this study.