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

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

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

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: gabapentin enacarbil

• Study Type: Interventional
• Enrollment (Actual): 346
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States
      • University of California Los Angeles
    • San Francisco, California, United States, 94103
      • Friends Research Institute
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Miller School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10025
      • Mount Sinai St. Luke's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75235
      • The University of Texas Southwestern Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects must meet each one of the following inclusion criteria in order to be eligible for participation in the study:

1. Be at least 21 years of age.
2. Have a current (past 12 months) DSM-5 diagnosis of AUD.
3. 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).
4. Be seeking treatment for problems with alcohol.

Additional will be evaluated in clinic.

Exclusion Criteria:

Evaluations will be conducted in clinic.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Collaborators: Arbor Pharmaceuticals, Inc.
• Investigators: Study Chair: Raye Z. Litten, Ph.D., National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: September 26, 2014
• First Submitted That Met QC Criteria: September 26, 2014
• First Posted (Estimate): September 30, 2014

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: alcohol dependence; alcohol use disorder; alcoholism; drinking alcohol
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: NCIG - 006