Role of BP1.3656 on Alcohol Responses

The current study will determine whether a novel pharmacotherapy, BP1. 3656, affects laboratory alcohol self-administration in participants with alcohol use disorder (AUD).

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: BP1.3656; Drug: Placebo

Detailed Description

The current study employs BP1.3656, a novel investigational compound with a track record for safety and tolerability in phase I clinical trials. When administered to mice, BP1.3656 was associated with increased metabolism of histamine and elevated brain dopamine and acetylcholine, suggestive of utility in psychiatric disorders including Alcohol Use Disorder (AUD).

This study is a Phase II laboratory-based trial of BP1 .3656 for AUD. 40 non-treatment seeking participants with AUD will be recruited. Participants will be randomly assigned to intervention with BP1 .3656 or placebo in a within-subject, crossover design. During each intervention period, outcome measures relating to alcohol motivation and self-administration will be assessed in the laboratory. It is hypothesized that relative to placebo, alcohol self-administration will be decreased by BP1 .3656.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 2S1
      • Center for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Fulfilling Diagnostic and Statistical Manual (DSM)-5 criteria for AUD with endorsement of 4-8 symptoms
• Average weekly consumption ≥ 14 standard drinks for women and ≥ 21 standard drinks for men over the past 3 months
• Willingness to take study medication and participate in laboratory sessions requiring alcohol administration
• Able to give written informed consent
• Certified as healthy by a comprehensive clinical assessment. Alanine transaminase (ALT) and aspartate aminotransferase (AST) levels should not be more than 1.2 times normal

Exclusion Criteria:

• Seeking treatment for alcohol use (or current efforts to cut down or seek treatment)
• A Clinical Institute Withdrawal Assessment (CIWA) score of 8+ upon initial assessment
• Current medical conditions or medications that contraindicate receiving the study drug (based on the study physician's assessment)
• Meeting criteria for a current substance use disorder aside from alcohol or nicotine
• Recent recreational drug use (assessed via urine toxicology screen)
• History of gross psychiatric or neurological impairment (e.g., schizophrenia, bipolar disorder, neurological disorders)
• Reported difficulty with intravenous procedures
• Self-report of significant alcohol-induced flushing after 1-2 drinks (a proxy for aldehyde dehydrogenase deficiency)
• Currently nursing or pregnant (females)
• Serious unstable medical condition
• Current use of medication that could increase the risk of BP1.3656B administration
• Having any clinical condition, drug sensitivity, or prior therapy which, in the investigator's opinion, makes the participant unsuitable for the study
• Any history of seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medication (BP1.3656); Participants will receive BP1.3656 in tablet form once daily at a dose of 30 µg/day for the first 4 days, followed by 60 µg/day for the remaining 10 days. If the highest dose is not tolerated, it will be lowered to 30 µg.	Drug: BP1.3656; BP1.3656 will be administered in tablet form once daily at a dose of 30 µg/day for the first 4 days of the intervention phase, followed by a dose increase to 60 µg/day for the remaining 10 days. If the highest dose is not tolerated, it will be lowered to 30 µg.
Placebo Comparator: Placebo pills; Participants will receive matching placebo pills for 14 days.	Drug: Placebo; Administered once daily in tablet form.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking study medication (BP1.3656).	Breath alcohol concentration (BrAC) test reading will be assessed	Measured during one self-administration session in the 2nd week of the 14-day study medication phase.
Peak breath alcohol concentration (mg%) during free-access alcohol self-administration while taking placebo.	Breath alcohol concentration (BrAC) test reading will be assessed	Measured during one self-administration session in the 2nd week of the 14-day placebo phase.
Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking study medication (BP1.3656).	Measured by number of button presses/work sets	Measured during one progressive-ratio self-administration session in the 2nd week of the 14-day medication phase
Motivation for alcohol completed during a progressive ratio alcohol self-administration session while taking placebo.	Measured by number of button presses/work sets	Measured during one progressive-ratio self-administration session in the 2nd week of the 14-day placebo-phase.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effects of alcohol during free-access and progressive ratio self-administration sessions while taking study medication (BP1.3656), as measured by the Biphasic Alcohol Effects Scale (0-10 scoring)	Two subscales (stimulant and sedative) with a 0-10 scoring where higher scores for stimulant subscale indicate increased stimulated effects from alcohol, while higher scores for sedative subscale indicate more sedated effects from alcohol.	Measured during each of two alcohol self-administration sessions (free-access, progressive ratio) completed in the 2nd week of the 14-day medication phase.
Subjective effects of alcohol (maximum reported stimulation and sedation from alcohol) during free-access and progressive ratio self-administration sessions while taking placebo, as measured by the Biphasic Alcohol Effects Scale (0-10 scoring)	Two subscales (stimulant and sedative) with a 0-10 scoring where higher scores for stimulant subscale indicate increased stimulation, while higher scores for sedative subscale indicate more sedated effects from alcohol.	Measured during each of two alcohol self-administration sessions (free-access, progressive ratio) completed in the 2nd week of the 14-day placebo phase.
Self-reported craving after a priming dose of alcohol during free-access and progressive ratio self-administration sessions while taking BP1.3656, as measured by the Alcohol Urge Questionnaire (1-7 scoring)	8 statements with score options ranging from Score of 1 = Strongly disagree to Score of 7 = Strongly Agree. Higher scores reflect greater craving.	Measured during each of 2 alcohol self-administration sessions (free-access, progressive ratio) completed in 2nd week of medication phase.
Self-reported craving after a priming dose of alcohol during free-access and progressive ratio self-administration sessions while taking placebo, as measured by the Alcohol Urge Questionnaire (1-7 scoring)	8 statements with score options ranging from Score of 1 = Strongly disagree to Score of 7 = Strongly Agree. Higher scores reflect greater craving.	Measured during each of 2 alcohol self-administration sessions (free-access, progressive ratio) completed in 2nd week of placebo phase.
Safety and tolerability of BP1.3656	Side effects of BP1.3656 will be assessed with the Systematic Assessment for Treatment Emergent Effects questionnaire (not reporting score on a scale) and the Pittsburgh Sleep Quality Index (19 items with 0-3 scoring, where higher scores indicate worse sleep quality).	During the free-access and progressive ratio sessions in the 2nd week of the 14-day study medication phase
Safety and tolerability of BP1.3656	Side effects of BP1.3656 will be assessed with the Systematic Assessment for Treatment Emergent Effects questionnaire (not reporting score on a scale) and the Pittsburgh Sleep Quality Index (19 items with 0-3 scoring, where higher scores indicate worse sleep quality).	During the free-access and progressive ratio sessions in the 2nd week of the 14-day study placebo phase
Weekly alcohol consumption during treatment with BP1 .3656	Drinks per week, as measured by the Timeline Follow-Back method	Measured during the 2nd week of the 14-day study medication phase
Weekly alcohol consumption during treatment with placebo	Drinks per week, as measured by the Timeline Follow-Back method	Measured during the 2nd week of the 14-day placebo phase

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Ethanol; Alcohol Drinking; Alcohol; Alcoholism; Alcohol Use Disorder; Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Substance-Related Disorders; Drinking Behavior; Self administration; BP1.3656B
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism
• Other Study ID Numbers: 072/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No