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

• ClinicalTrials.gov Identifier: NCT02252536
• Recruitment Status: Completed
• First Posted: September 30, 2014
• Results First Posted: September 21, 2018
• Last Update Posted: November 14, 2018
• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Collaborator: Arbor Pharmaceuticals, Inc.
• Information provided by (Responsible Party): National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Tracking Information

• First Submitted Date: September 26, 2014
• First Posted Date: September 30, 2014
• Results First Submitted Date: April 9, 2018
• Results First Posted Date: September 21, 2018
• Last Update Posted Date: November 14, 2018
• Study Start Date: June 2015
• Actual Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 20, 2018)

Percentage of Subjects With no Heavy Drinking Days (PSNHDD) [ Time Frame: Weeks 22-25 ]

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).

Original Primary Outcome Measures (submitted: September 26, 2014)

Percentage of subjects with no heavy drinking days (PSNHDD) [ Time Frame: Weeks 18-25 ]

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 8 weeks of treatment, among patients with Alcohol Use Disorder (AUD).

Current Secondary Outcome Measures (submitted: October 15, 2018)

• Percentage of Subjects Abstinent From Alcohol (Key Secondary Endpoint) [ Time Frame: Weeks 22-25 ]
  Timeline Follow-back drinking data is used to calculate the % of subjects that report not drinking alcohol during weeks 22-25
• Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 1-level [ Time Frame: Weeks 22-25 ]
  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
• Percentage of Subjects With a World Health Organization (WHO) Drinking Risk Category Decrease of at Least 2-levels [ Time Frame: Weeks 22-25 ]
  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
• Percentage of Days Abstinent Per Week [ Time Frame: Weeks 22-25 ]
  Timeline Follow Back daily drinking data used to calculate the % of days abstinent per week.
• Percentage of Heavy Drinking Days Per Week [ Time Frame: Weeks 22-25 ]
  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
• Weekly Mean Number of Drinks Per Week [ Time Frame: Weeks 22-25 ]
  Timeline Follow Back data used to calculate the weekly mean number of drinks per week
• Weekly Mean Drinks Per Drinking Day [ Time Frame: Weeks 22-25 ]
  Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day
• Cigarettes Per Week Among Smokers [ Time Frame: Weeks 22-25 ]
  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)?".
• Alcohol Craving Score [Alcohol Craving Scale - Short Form (ACQ-SR-R)] [ Time Frame: Weeks 24 and 26 ]
  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
• Alcohol Related Consequences (ImBIBe) Score [ Time Frame: Weeks 24 and 26 ]
  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
• Pittsburgh Sleep Quality Index (PSQI) Score [ Time Frame: Week 26 ]
  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.
• Beck Anxiety Inventory (BAI) Score [ Time Frame: Week 26 ]
  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
• Beck Depression Inventory - II [ Time Frame: Week 26 ]
  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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: HORIZANT (Gabapentin Enacarbil Extended-Release Tablets) for the Treatment of Alcohol Use Disorder
• Official Title: 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
• Brief Summary: The purpose of this study is to determine whether gabapentin enacarbil is effective in the treatment of problems with alcohol.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alcohol Use Disorder

Intervention

• Drug: gabapentin enacarbil
  Horizant Extended Release Tablets, 600 mg, white to off-white, oval shaped tablets, taken 2 times per day
  Other Name: Horizant Extended Release Tablets
• Drug: Placebo
  Placebo tablet, white to off-white, oval shaped tablets, taken 2 times per day

Study Arms

• Placebo Comparator: Sugar Pill
  Matching placebo, sugar pill
  Intervention: Drug: Placebo
• Active Comparator: Gabapentin Enacarbil
  600 mg Gabapentin Enacarbil (Horizant)
  Intervention: Drug: gabapentin enacarbil

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 26, 2014): 346
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 2017
• Actual Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02252536
• Other Study ID Numbers: NCIG - 006
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Original Study Sponsor: Same as current
• Collaborators: Arbor Pharmaceuticals, Inc.

Investigators

• Study Chair: Raye Z. Litten, Ph.D.; National Institute on Alcohol Abuse and Alcoholism (NIAAA)

• PRS Account: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Verification Date: October 2018