A Novel Compound for Alcoholism Treatment

This is an interventional treatment trial for Alcoholism focused on measuring Alcoholism, Ghrelin, Ghrelin Antagonism Read More

• INCLUSION CRITERIA:
• Males or females 21-65 years old (inclusive);
• Heavy drinking defined as on average at least 21 drinks per week for men or at least 14 drinks for women based on the timeline follow-back (TLFB) done at screening.
• Be in good health as confirmed by medical history, physical examination, ECG, blood/urine lab tests;

• Female subjects must be of non childbearing potential as defined by at least one of the following criteria:

  • Females 45 65 years old, who are menopausal, defined as follows:

    • Females who are between 45 55 years old: they will be considered menopausal if they satisfy all the following three requirements during screening: 1) they are in amenorrhea, defined as absence of menstruation for the previous 12 months; 2) they have a negative urine pregnancy test; and 3) they have a serum FSH level within the laboratory s reference range for postmenopausal females.
    • Females who are between 56 65 years old: they will be considered menopausal if they are in amenorrhea, defined as absence of menstruation for the previous 12 months before screening.
  • OR
  • Females 21-65 years old, who have a documented hysterectomy and/or bilateral oophorectomy.
  • All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy) will be considered to be of childbearing potential.

• Male subjects must use one of the following methods of contraception from the first dose of study medication and until 28 days after dosing:

  • Abstinence.

  • A condom AND one of the following:

    • Vasectomy for more than 6 months.

    • Female partner who meets one of the following conditions:

      • Has had a tubal ligation, hysterectomy, or bilateral oophorectomy;
      • Is post menopausal;

      • Uses one of the following forms of contraception:

        • Copper or hormonal containing IUD;
        • Spermicidal foam/gel/film/cream/suppository;
        • Diaphragm with spermicide;
        • Oral contraceptive;
        • Injectable progesterone;
        • Subdermal implant.

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.