Pitolisant Effects on Alcohol Self-Administration in Heavy Drinkers

NCT04596267 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: H-409591R21AA028864-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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

Conditions

Alcohol Use Disorder; Alcohol Drinking

Keywords

pitolisant; Wakix

Outcome Measures

Primary Outcomes (9)

• Alcohol Consumption in Alcohol Self-Administration Trials

  Alcohol consumption will be measured by using a graduated cylinder to determine the amount of alcohol given to the subject that was not consumed. This outcome will be measured as standard drink units (SDU). A standard drink contains approximately 0.6 fluid ounces of pure alcohol. Lower SDUs are favorable.

  2.6 hours

• Alcohol Consumption (BAC): Observation Period, Minute 10

  Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable

  1 minute

• Alcohol Consumption (BAC): Observation Period, Minute 20

  Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.

  1 minute

• Alcohol Consumption (BAC): Observation Period, Minute 30

  Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.

  1 minute

• Alcohol Consumption (BAC): Observation Period, Minute 40

  Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.

  1 minute

• Alcohol Consumption (BAC): Self-administration Block 1, Minute 30

  Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.

  1 minute

• Alcohol Consumption (BAC): Self-administration Block 1, Minute 60

  Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.

  1 minute

• Alcohol Consumption (BAC): Self-administration Block 2, Minute 30

  Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.

  1 minute

• Alcohol Consumption (BAC): Self-administration Block 2, Minute 60

  Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.

  1 minute

Secondary Outcomes (30)

• Alcohol Craving During 12-day Drug Exposure

  12 days

• Alcohol Consumption During the 12-day Drug Exposure

  12 days

• Alcohol-induced Stimulation: Observation Period, Minute 10

  1 minute

• Alcohol-induced Stimulation: Observation Period, Minute 20

  1 minute

• Alcohol-induced Stimulation: Observation Period, Minute 30

  1 minute

Study Arms (2)

Pitolisant

EXPERIMENTAL

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.

Drug: Pitolisant

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Pitolisant DRUG

8.9mg Pitolisant for 5 days

Also known as: wakix

Pitolisant

Placebo DRUG

Inert ingredients

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years of age
• Able to verify age with a state or federal picture identification
• 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)
• Reports at least one episode of binge drinking (\>3 drinks for women, \>4 drinks for men) in the 28 days prior consent.
• Meets DSM-5 criteria for mild alcohol use disorder or greater severity.
• Has a smartphone to complete medication exposure period study assessments.

You may not qualify if:

• Seeking treatment for alcohol problems
• Clinical Institute Withdrawal Assessment at ≥10
• 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
• If female, pregnant, nursing, have plans to become pregnant
• If female, does not agree to use an accepted form of birth control
• Has a medical contraindication to the use of pitolisant
• Has medical or mental condition for which further alcohol exposure at the planned dose range would be contraindicated
• Current risk of suicidality (MINI suicidality score greater than 8 (low risk) or Yes to the ideation question #4 of the C-SSRS)
• BMI is greater than 40 or less than 18
• Impaired renal function (GFR \<80 mL/min)
• Have a history of any clinically significant renal or hepatic disease
• Child-Pugh Score equal to or greater than Class B (evaluated based on presence or absence of encephalopathy and ascites, INR, bilirubin, and albumin) \[https://www.mdcalc.com/child-pugh-score-cirrhosis-mortality\]
• 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
• 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
• Has received alcohol counseling or other non-pharmacologic intervention to treat AUD in the past 90 days

Sponsors & Collaborators

• Boston Medical Center: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Boston University Psychiatry Research Center, Clinical Studies Unit

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Alcoholism; Alcohol Drinking

Interventions

pitolisant

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Drinking Behavior; Behavior

Limitations and Caveats

Recruitment was impacted by COVID-19 restrictions on human subject research, leading to a smaller number of subjects analyzed than planned. This study start date was also delayed due to problems securing the medication supply.

Results Point of Contact

• Title: Dr. Eric Devine
• Organization: Boston Medical Center

eric.devine@bmc.org

617-418-7888

Study Officials

• Eric Devine, PhD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is double-blind. Medications are over-encapsulated.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 15, 2020
• First Posted: October 22, 2020
• Study Start: September 13, 2021
• Primary Completion: February 3, 2023
• Study Completion: February 3, 2023
• Last Updated: December 4, 2023
• Results First Posted: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)