Role of BP1.3656 on Alcohol Responses

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

Detailed Description
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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.

Official Title
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Role of BP1.3656 on Alcohol Responses

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: BP1.3656
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This will be a within-subjects, counterbalanced, crossover trial with a washout period. Participants will receive either placebo or the interventional drug BP1.3656 during the initial 14-day phase of the study and receive the other intervention during the second 14-day phase of the study. The washout period will last a minimum of 14 days. Participants will come in to the laboratory on two separate days near the end of each intervention phase to complete alcohol self-administration sessions.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medication (BP1.3656)<br>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<br>* 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.<br>|
| Placebo Comparator: Placebo pills<br>Participants will receive matching placebo pills for 14 days. | Drug: Placebo<br>* Administered once daily in tablet form.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ethanol, Alcohol, Self administration, BP1.3656B, Alcohol Use Disorder, Alcoholism, Alcohol Drinking, Drinking Behavior, Alcohol-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders