Pitolisant Effects on Alcohol Self-Administration in Heavy Drinkers

NCT ID: NCT04596267

Last Updated: 2023-12-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-13
• Study Completion Date: 2023-02-03

Brief 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

Detailed 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.

Conditions

Alcohol Use Disorder; Alcohol Drinking

Keywords

pitolisant; Wakix

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pitolisant

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.

Group Type: EXPERIMENTAL

Pitolisant

Intervention Type: DRUG

8.9mg Pitolisant for 5 days

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Inert ingredients

Interventions

Pitolisant

8.9mg Pitolisant for 5 days

Intervention Type: DRUG

Placebo

Inert ingredients

Intervention Type: DRUG

Other Intervention Names

wakix

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.).

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Boston Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Devine, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Medical Center

Locations

Boston University Psychiatry Research Center, Clinical Studies Unit

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R21AA028864-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H-40959

Identifier Type: -

Identifier Source: org_study_id