Pitolisant Effects on Alcohol Self-Administration in Heavy Drinkers
Condition: Alcohol Use Disorder; Alcohol Drinking
MeSH terms: Alcoholism; Alcoholic Intoxication; Alcohol Drinking
Intervention: Pitolisant; Placebo
Intervention description: 8.9mg Pitolisant for 5 days; Inert ingredients
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a double-blind, randomized, placebo-controlled, crossover design trial that will test the effect of pitolisant on alcohol self-administration and craving following a priming dose of alcohol.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This study is double-blind. Medications are over-encapsulated.
Enrollment: 9.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: pitolisant; Wakix

Summary:

      This is a double-blind, randomized, placebo-controlled, crossover design trial that will test
      the effect of pitolisant on alcohol self-administration and craving following a priming dose
      of alcohol. The specific objective of this proposal is to determine whether pitolisant has
      effects on alcohol consumption and craving
    

Eligibility criteria:

        Inclusion Criteria:

          1. 21-55 years of age

          2. Able to verify age with a state or federal picture identification

          3. Exceeds safe weekly drinking limits during the 28 days prior to consent (average of 14
             drinks for women or 21 drinks for men per week)

          4. Reports at least one episode of binge drinking (>3 drinks for women, >4 drinks for
             men) in the 28 days prior consent.

          5. Meets DSM-5 criteria for mild alcohol use disorder or greater severity.

          6. Has a smartphone to complete medication exposure period study assessments.

        Exclusion Criteria:

          1. Seeking treatment for alcohol problems

          2. Clinical Institute Withdrawal Assessment at ≥10

          3. DSM-5 diagnosis of current major depression, bipolar disorder, schizophrenia,
             bulimia/anorexia, dementia, insomnia disorder or a substance use disorder other than
             alcohol, nicotine, marijuana or caffeine

          4. If female, pregnant, nursing, have plans to become pregnant

          5. If female, does not agree to use an accepted form of birth control

          6. Has a medical contraindication to the use of pitolisant

          7. Has medical or mental condition for which further alcohol exposure at the planned dose
             range would be contraindicated

          8. Current risk of suicidality (MINI suicidality score greater than 8 (low risk) or Yes
             to the ideation question #4 of the C-SSRS)

          9. BMI is greater than 40 or less than 18

         10. Impaired renal function (GFR <80 mL/min)

         11. Have a history of any clinically significant renal or hepatic disease

         12. Child-Pugh Score equal to or greater than Class B (evaluated based on presence or
             absence of encephalopathy and ascites, INR, bilirubin, and albumin)
             [https://www.mdcalc.com/child-pugh-score-cirrhosis-mortality]

         13. Have a clinically significant ECG as determined by the investigator or abnormal ECG
             heart rate (<45 or >100 bpm) or QTc interval corrected for heart rate using the
             Fridericia formula (QTcF) > 450 msec

         14. Have a history of cardiac arrhythmias or who for other reasons are at risk for
             developing Torsade de Pointes including those with bradycardia, hypokalemia, and
             congenital QT interval prolongation

         15. Has received alcohol counseling or other non-pharmacologic intervention to treat AUD
             in the past 90 days

         16. Has taken medications that are used to treat AUD in the past 90 days

         17. Has urine toxicology results positive for cocaine, opioids, amphetamines,
             buprenorphine, methadone, methamphetamines, oxycontin, barbiturates, or
             benzodiazepines.

         18. Subject is taking a medication which will significantly alter drug metabolism (e.g.,
             strong CYP2D6 inhibitors, strong CYP3A4 inducers, or H1 receptor antagonists that
             cross the blood barrier (e.g. diphenhydramine or meclizine).

         19. Subject is known to be a poor CYP2D6 metabolizer.

         20. Subject is unable to comfortably abstain from nicotine for a period of 8 hours.

         21. Has Chronic Obstructive Pulmonary Disease (COPD), history of solid organ transplant,
             sickle cell disease, severe heart disease or other health condition for which exposure
             to COVID-19 represents an unreasonable risk as determined by the study staff physician
             using accepted COVID-19 guidance (e.g. Centers for Disease Control, etc.).