Open Label Pilot Study of Perampanel for the Treatment of Alcohol Use Disorder

The purpose of this research study is to test the safety, tolerability, and effectiveness of the drug Perampanel when used in persons who drink and wish to stop drinking. Perampanel has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures but has not yet been approved to treat alcohol use disorders. For this reason, it is considered an investigational drug. Some people in this study will receive Perampanel alone and some people will receive Perampanel and Disulfiram, this will be determined by the pharmacy.

Study Overview

• Status: Completed
• Conditions: Alcohol Disorders
• Intervention / Treatment: Drug: Perampanel Tablet; Drug: Disulfiram

Detailed Description

Participants will be asked to take a medication (Perampanel or Perampanel + Disulfiram) every day for approximately 8 weeks and have weekly study visits. At these visits, participants will be asked questions about their medical history, drinking behavior and life events, have bloodwork checked routinely, have regular medication counseling, and perform some computer tasks. Throughout the study, there will be regular phone calls from staff. Participants will also be asked to use a device called "Soberlink" which is like an at-home breathalyzer test to help track progress throughout the study.

Participants will be randomly assigned (like the flip of a coin) to receive either Perampanel alone or Peramanel and Disulfiram.

Participation in this study will last up to 10 weeks. Approximately 20 individuals will participate in this study.

This study will sequence all or part of participant's DNA. This is a necessary part of the study.

Before starting the study, participants may be referred to an alcohol detoxification program (medical treatment of an alcoholic), if clinically indicated.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University Inst. for Drug and Alcohol Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women ages 21-70 with DSM-5 AUD;
2. regular heavy drinkers as defined by averaging ≥ 2 heavy drinking days per week over the 60 days baseline pre-treatment TLFB, and recognize a need to completely stop drinking;
3. willingness to provide written, informed consent to participate in the study;
4. Individuals with LFTs that are no more than 2-3 times above the normal levels and with a Child-Pugh score of no greater than 5 will be included and
5. women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or tubal ligation or <2 years postmenopausal), must be non-lactating, practicing a reliable method of birth control, and have a negative serum pregnancy test prior to initiation of treatment.

Exclusion Criteria:

1. a current, clinically significant physical disease [i.e., neurologic, renal, pulmonary, cardiovascular, hepatic] on the basis of medical history, physical examination, or routine laboratory evaluation that, in the context of the study would represent a risk to the subject, or significant laboratory abnormalities related to hepatic function such as marked elevations of hepatic aminotransferase levels (i.e., AST and ALT) or direct bilirubin;
2. history of renal compromise or current renal disease (as evidenced by serum creatinine above our laboratory's reference limit of 1.7 mg/dL;
3. history of seizure disorder;
4. use of any of a number of medications that might prominently influence drinking patterns or cause risk of harm or injury (e.g., other anticonvulsants, medications to treat AUD, opioid pain medication), currently taking CNS depressants (e.g. benzodiazepines, barbiturates, sedating antihistamines;
5. schizophrenia, bipolar disorder, current major depressive episode, or substantial suicide or violence risk on the basis of history or psychiatric examination;
6. currently dependent on stimulants, opioids or sedatives;
7. subjects with any substantial alcohol withdrawal will be required to be detoxified by regular clinical services prior to study entry;
8. are currently taking any medication that is a moderate to strong CYP3A4 inhibitor or inducer if participants are required to initiate these medications by an outside provider during the course of this study, they will be tapered off the study regimen and we will have them terminate early)
9. are taking phenytoin or warfarin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: perampanel by itself	Drug: Perampanel Tablet; Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups
Active Comparator: Perapanel with Disulfiram	Drug: Perampanel Tablet; Subjects will be titrated over 3 weeks to a target dose of 8mg perampanel daily in both groups; Drug: Disulfiram; Disulfiram will be kept at 250mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Abstinent Days	Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Participants will be accessed for the full 12 week titration plus treatment period. However, for the purposes of the study, the percent of days the participant was abstinent will be calculated and reported only for the 8 week active treatment period.	End of treatment, up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Alcohol Craving	Alcohol craving will be assessed using the Alcohol Urge Questionnaire (AUG). The AUG is an 8-item survey asking participants to rate their craving for alcohol on a 1 to 7 scale. The answers are summed yielding a score ranging from 7 to 56 with higher scores indicated higher alcohol craving.	Baseline to end of treatment, up to 12 weeks
Percent Heavy Drinking Days	Participant will report the number of alcoholic drinks they consumed during the previous weeks period. Based on participant report, the percent of days the participant drank heavily will be calculated over the 8 week active treatment period.	End of treatment, Up to 8 weeks

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Albert Arias, MD, PhD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): August 11, 2021
• Study Completion (Actual): August 11, 2021

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): October 7, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Alcoholism; Alcohol-Related Disorders; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Alcohol Deterrents; Acetaldehyde Dehydrogenase Inhibitors; Disulfiram
• Other Study ID Numbers: HM20015846; R21AA026681 (U.S. NIH Grant/Contract)

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