HORIZANT (Gabapentin Enacarbil Extended-Release Tablets) for the Treatment of Alcohol Use Disorder

Study Overview
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Brief Summary
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The purpose of this study is to determine whether gabapentin enacarbil is effective in the treatment of problems with alcohol.

Official Title
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Randomized, Double Blind, Placebo-Controlled Trial of the Safety and Efficacy of HORIZANT (Gabapentin Enacarbil) Extended-Release Tablets for the Treatment of Alcohol Use Disorder

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: gabapentin enacarbil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet each one of the following inclusion criteria in order to be eligible for participation in the study: Be at least 21 years of age. Have a current (past 12 months) DSM-5 diagnosis of AUD. Have a BAC by breathalyzer equal to 0.000 when s/he signed the informed consent document (either just prior to or immediately after signing consent). Be seeking treatment for problems with alcohol. Additional will be evaluated in clinic. Exclusion Criteria: Evaluations will be conducted in clinic.

Ages Eligible for Study
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Minimum Age: 21 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar Pill<br>Matching placebo, sugar pill | Drug: Placebo<br>* Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day<br>|
| Active Comparator: Gabapentin Enacarbil<br>600 mg Gabapentin Enacarbil (Horizant) | Drug: gabapentin enacarbil<br>* Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day<br>* Other names: Horizant Extended Release Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With no Heavy Drinking Days (PSNHDD) | The primary objective of the study is to compare the efficacy of HORIZANT (gabapentin enacarbil) Extended-Release Tablets 600 mg twice daily (BID) with matched placebo on the primary alcohol consumption outcome endpoint, percentage of subjects with no heavy drinking days (PSNHDD) during the last 4 weeks of treatment, among patients with Alcohol Use Disorder (AUD). | Weeks 22-25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Abstinent From Alcohol (Key Secondary Endpoint) | Timeline Follow-back drinking data is used to calculate the % of subjects that report not drinking alcohol during weeks 22-25 | Weeks 22-25 | 
| Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 1-level | Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows: Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g | Weeks 22-25 | 
| Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 2-levels | Timeline Follow Back data is used to calculate the % of participants that decrease at least 1-level WHO drinking risk category. The WHO has developed a drinking risk categorical scale that can be used in a responder analysis approach to assess clinically relevant decreases in alcohol consumption (Aubin et al-2015). The WHO 1- and 2-level decrease endpoints are the percentage of subjects experiencing at least 1- and 2-level decrease in WHO levels of alcohol consumption, respectively, from the level at baseline (the period including the 28 days before screening) to the level during the last 4 weeks of the maintenance phase (Study Weeks 22-25). The WHO levels are as follows: Males Females Low Risk 1 to 40g 1 to 20g Medium Risk 41 to 60g 21 to 40g High Risk 61 to 100g 41 to 60g Very High Risk 101+g 61+g | Weeks 22-25 | 
| Percentage of Days Abstinent Per Week | Timeline Follow Back daily drinking data used to calculate the % of days abstinent per week. | Weeks 22-25 | 
| Percentage of Heavy Drinking Days Per Week | Timeline Follow Back data used to calculate the % of heavy drinking days per week. Heavy drinking is 4+ drinks per day for females and 5+ drinks per day for males | Weeks 22-25 | 
| Weekly Mean Number of Drinks Per Week | Timeline Follow Back data used to calculate the weekly mean number of drinks per week | Weeks 22-25 | 
| Weekly Mean Drinks Per Drinking Day | Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day | Weeks 22-25 | 
| Cigarettes Per Week Among Smokers | A quantity frequency interview of three questions to assess cigarette smoking behavior and other tobacco/nicotine containing products use during the study: 1) Over the past week, on how many days did you smoke cigarettes?, 2) On the days you smoked during the past week, how many cigarettes did you smoke on average?, and 3) Have you used any other tobacco or nicotine containing products besides cigarettes in the past week (e.g., cigars, cigarellos, pipes, bidis, or smokeless tobacco such as pan, chewing tobacco, or snuff, or nicotine replacement therapies such as patch or gum)?. | Weeks 22-25 | 
| Alcohol Craving Score [Alcohol Craving Scale - Short Form (ACQ-SR-R)] | The ACQ-SR-R contains 12-items adapted from the 47-item ACQ-NOW developed by Singleton et al (1994) to assess craving for alcohol among alcohol users in the current context (right now). Each item has a 1 to 7 raw score (from strongly disagree to strongly agree). Items 3, 8, and 11 are reverse keyed. A general craving index is derived by summing all items and dividing by 12. Minimum score is 1 and maximum score is 7. Higher scores are indicative of higher craving. Mixed effects models as stated in Section 9.4.3 of the SAP will be generated for the total score and for the 4 subscales. Covariates for these models will be identified | Weeks 24 and 26 | 
| Alcohol Related Consequences (ImBIBe) Score | ImBIBe is a 15-item questionnaire in which the subject responds on a 5-point scale (0-4) responses to questions on the consequences of alcohol use. This scale was adapted from the Drinker Inventory of Consequences questionnaire based on FDA recommendations on patient reported outcomes (Miller & Tonigen-1995). The potential range is 0-60. A higher score indicates a worse outcome. The questions are added together. A question that is missing is imputed with the average value of all other questions in the questionnaire.The total score is the sum of the individual item scores. Mixed effects models as stated in Section 9.4.3 will be generated for the total score. Covariates for these models will be identified | Weeks 24 and 26 | 
| Pittsburgh Sleep Quality Index (PSQI) Score | The PSQI is a 19-item questionnaire assessing the subject's overall sleep experience in the past 30 days (Buysse et al-1989). The lower the overall score, the better the person sleeps. The tool has an adequate internal reliability, validity and consistency for clinical and community samples of the various populations. Range is (0-21); >6 indicative of poor sleep quality. | Week 26 | 
| Beck Anxiety Inventory (BAI) Score | The BAI consists of 21 questions about how the subject has been feeling in the last week, expressed as common symptoms of anxiety (such as numbness and tingling, sweating not due to heat, and fear of the worst happening). This inventory was designed to minimize the overlap with depression scales (Beck et al-1988).The BAI has a maximum score of 63. The standardized cutoffs for anxiety severity are: 0-7: minimal level of anxiety 8-15: mild anxiety 16-25: moderate anxiety 26-63: severe anxiety | Week 26 | 
| Beck Depression Inventory - II | The BDI-II is a 21-item multiple choice questionnaire that is used for measuring the severity of depression (Beck et al-1966). Each item is scored on a scale value of 0 to 3. The standardized cutoffs for depression severity are: 0-13: minimal depression 14-19: mild depression 20-28: moderate depression 29-63: severe depression | Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol use disorder, alcoholism, alcohol dependence, drinking alcohol