Medication Development in Alcoholism: Suvorexant Versus Placebo
Condition: Alcohol Use Disorder (AUD)
MeSH terms: Alcoholism
Intervention: Suvorexant 20 mg; Placebo oral tablet
Intervention description: Single-dose administration of 20 mg suvorexant given on an inpatient clinical research unit; Single-dose administration of placebo given on an inpatient clinical research unit
Intervention MeSH terms: Suvorexant
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel Assignment, Double-Blind, Randomized Stratified at randomization based on sex and Pittsburgh Sleep Quality Index Total Score (PSQI) greater than or equal to 5 versus less than 5.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The primary hypotheses under test are that alcohol dependent subjects treated with suvorexant
      will report decreased craving for alcohol following alcohol exposure in the laboratory and
      report significantly less drinking under naturalistic conditions, than those treated with
      placebo. Suvorexant (Belsomra®) received approval by the FDA in 2014 for treatment of
      insomnia. To control for any effect of pre-existing sleep disturbance for which suvorexant
      may be indicated, subjects will be stratified on the basis of a Pittsburgh Sleep Quality
      Index total score of > 5 versus <5. Subjects were also stratified by sex.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female volunteers, 18-65 years of age.

          -  Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
             criteria for current alcohol use disorder of moderate or greater severity (AUD-MS).

          -  In the month prior to screening, reports drinking ≥ 21 standard drinks per week if
             male, ≥ 14 if female, with at least one heavy drinking day (≥ 5 males, ≥ 4 females)
             per week.

          -  Subjects will not be seeking treatment because the medication studies are not
             treatment trials, and to avoid exposing treatment-seekers to alcohol cues

          -  Subjects must be abstinent a minimum of 3 days (but not more than 7 days) prior to the
             human lab session.

          -  Negative blood alcohol content (BAC) and a Clinical Institute Withdrawal Assessment
             (CIWA) score of < 9 at time of randomization and lab session to eliminate acute
             alcohol or withdrawal effects on dependent measures.

          -  In acceptable health in the judgment of the study physician, on the basis of
             interview, medical history, physical exam, EKG, routine urine and blood chemistry.

          -  Subjects with a history of depression, who have been on a stable dose of
             anti-depressant medication for at least 3 months, and do not meet current DSM-5
             criteria for depression or anxiety.

          -  Females with childbearing potential must have a negative pregnancy test on the
             screening and randomization visits and agree to use effective birth control for the
             duration required by a given study.

          -  Able to provide informed consent and understand questionnaires and study procedures in
             English.

          -  Willing to comply with the provisions of the protocol and take oral medication.

        Exclusion Criteria:

          -  Meets DSM-5 criteria for a major psychiatric disorder, including mood or anxiety
             disorders or substance use disorders other than alcohol or nicotine, or, mild cannabis
             use disorder

          -  Has a urine drug screen (UDS) positive for substances of abuse other than alcohol or
             marijuana

          -  Significant medical disorders that will increase potential risk or interfere with
             study participation as determined by the study physician.

          -  Liver function tests more than 3 times the upper limit of normal or elevated
             bilirubin.

          -  Subjects taking digoxin or CYP3A inhibitors or inducers, metabolism by CYP3A is the
             major elimination pathway for suvorexant.

          -  Treatment within the month prior to screening with (1) an investigational drug, (2)
             medications which may negatively interact with study medications, or (3) drugs that
             may influence study outcomes (e.g., disulfiram [Antabuse], naltrexone [ReVia],
             acamprosate [Campral], or anticonvulsants).

          -  Ongoing treatment with medications that may increase risk, including prescribed,
             over-the-counter, and herbal preparations, as determined by the study physician.

          -  Sexually active female subjects with childbearing potential who are pregnant, nursing,
             or refuse to use effective methods of birth control for the duration of the study.

          -  No fixed domicile and/or no availability by home or mobile telephone.

          -  History of hypersensitivity to the study drug or the ingredients.

          -  Failure to take double-blind medication as prescribed.