Pitolisant Effects on Alcohol Self-Administration in Heavy Drinkers

Boston Medical Center (BMC)

Status and phase: Terminated; Phase 1

Conditions: Alcohol Use Disorder; Alcohol Drinking

Treatments: Drug: Placebo; Drug: Pitolisant

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04596267

1R21AA028864-01 (U.S. NIH Grant/Contract)

H-40959

Details and patient eligibility

About

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

Full description

The present proposal is intended to answer the call for accelerating drug development by exploring the potential of a novel anticonvulsant, Pitolisant as a candidate medication for the treatment of AUD. Pitolisant is an H-3 receptor inverse agonist that is FDA-approved for treating narcolepsy which has been found to have effects of on alcohol craving and consumption in preclinical studies. The aims of this study are to test the effects of Pitolisant on alcohol self-administration and craving among a sample of non-treatment seeking heavy drinkers. The effects of 5-days of pitolisant (8.9mg) or placebo will be evaluated in a human laboratory using an alcohol self-administration methodology. In this within-subjects crossover design, heavy drinkers (N=28) will be randomized to the order of exposure (Pitolisant or placebo) prior to completing two alcohol self-administration trials. Subjects will receive a priming drink of alcohol and will have access to 8 alcoholic drinks over a 2-hour period. The investigators anticipate that subjects will consume less alcohol during an alcohol self-administration trial when receiving Pitolisant compared to when they are receiving placebo. Significant Pitolisant-induced reductions in the quantity of alcohol self-administered will be considered to be an indication that this drug may have value as an AUD medication. This study may provide a rationale for phase II clinical studies testing Pitolisant with a treatment-seeking AUD population.

Enrollment: 9 patients

Sex: All

Ages: 21 to 55 years old

Volunteers: No Healthy Volunteers

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.).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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9 participants in 2 patient groups, including a placebo group

Pitolisant

Experimental group

Description:

Subjects will take an 8.9 mg dose (two 4.45 mg pills) of pitolisant once per day on day 1 through 4. On day 5, 8.9 mg will be taken in front of staff prior to an alcohol self administration trial.

Treatment:

Drug: Pitolisant

Placebo

Placebo Comparator group

Description:

Subjects will take an placebo once per day on day 1 through 4. On day 5, a placebo will be taken in front of staff prior to an alcohol self administration trial.

Treatment:

Drug: Placebo