Rapid Determination Of The Clinical Utility Of Perampanel For The Treatment Of Alcohol Dependence

NCT02120365 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: HM200144461407014397R21AA026681
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine whether perampanel alters the response to alcohol for heavy drinkers. It is hypothesized that perampanel will reduce the rewarding and reinforcing properties of alcohol in the laboratory setting.

Conditions

Alcoholism

Keywords

Alcoholism; Heavy Drinking; Perampanel

Outcome Measures

Primary Outcomes (3)

• Biphasic Alcohol Effects Scale (BAES): Stimulant Subscale

  A 14-item scale with 7 items designed to assess stimulant effects from alcohol intoxication and 7 items developed to measure the sedative effects of alcohol. This scale was selected as a primary outcome measure because it is sensitive to the effect of alcohol. This outcome item reports the Stimulant Subscale results analyzed with mixed models. Each item can be scored a minimum of zero (0) or up to 10 with the 10 representing feeling more or the most intoxicated in that item's description (e.g., "excited"). The minimum score is 0 and the maximum score is 70. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).

  98 minutes

• Biphasic Alcohol Effects Scale (BAES)- Sedative Subscale

  A 14-item scale with 7 items designed to assess stimulant effects from alcohol intoxication and 7 items developed to measure the sedative effects of alcohol. This scale was selected as a primary outcome measure because it is sensitive to the effect of alcohol. This entry item show the results for the sedative subscale evaluated in mixed models. Each item can be scored a minimum of zero (0) or up to 10 with the 10 representing feeling more or the most intoxicated in that item's description (e.g., "sedated"). The minimum score is 0 and the maximum score is 70. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes).

  98 minutes

• Drug Effects Questionaire (DEQ)

  consists of four items that measure current alcohol effects: 'feel alcohol', 'feel high', 'like alcohol', and 'want more alcohol'. For the time frame, the values at different time points were combined (averaged) into a single value that represents the effect during the time interval of interest (12 to 110 minutes). There are five items on the scale with scores of 0 to 100, and the total score is used by averaging all five items, thus, the minimum total score on the scale is 0 and the maximum is 100. The lowest score 0 represents "not at all" or not experiencing any drug effects from alcohol, and 100 represents "extremely" experiencing alcohol effects.

  98 min

Secondary Outcomes (3)

• Alcohol Urge Questionnaire (AUQ)

  98 min

• Side Effect Questionnaire (SEQ)

  98 minutes

• Profile of Mood States (POMS) 2 Short Version Total Score

  98 minutes

Study Arms (3)

Perampanel 6mg

EXPERIMENTAL

Participants will have 3 test days each, 2 weeks apart, in a randomized order, following either pretreatment with daily perampanel 2mg days prior to each test day, and then observed dosing moderate 6mg dose perampanel in the lab 1 hour before a one-time alcohol infusion . Each lab session occurs exactly a week after starting the medication for that round. The wash out period between lab test session phases will be 7-10 days. Subjects will receive 2 days of 2mg perampanel after each lab to taper down (included in the washout period). The next appointment will be brief at the start of the next phase, at which point the next week of low dose perampanel or placebo will be started. With the washout period and the 7 day taper of the next phase, the actual lab sessions will occur 14-17 days apart. All test days will involve administration of alcohol with the same 3 target doses \[target Breath Alcohol Concentration (BrAc) =20mg%, 60mg%, and 100mg%\] in a step-wise fashion.

Drug: Perampanel

Placebo

PLACEBO COMPARATOR

Participants will have 3 test days each, 2 weeks apart, in a randomized order, following either pretreatment with placebo 7 days prior to each test day, and then observed dosing of placebo in the lab 1 hour before a one-time alcohol infusion . Each lab session occurs exactly a week after starting the medication for that round. The wash out period between lab test session phases will be 7-10 days. Subjects will receive 2 days of 2mg perampanel after each lab to taper down (included in the washout period). The next appointment will be brief at the start of the next phase, at which point the next week of low dose perampanel or placebo will be started. With the washout period and the 7 day taper of the next phase, the actual lab sessions will occur 14-17 days apart. All test days will involve administration of alcohol with the same 3 target doses \[target Breath Alcohol Concentration (BrAc) =20mg%, 60mg%, and 100mg%\] in a step-wise fashion.

Drug: Placebo

Perampanel 10 mg

EXPERIMENTAL

Participants will have 3 test days each, 2 weeks apart, in a randomized order, following either pretreatment with daily perampanel 2mg 7 days prior to each test day, and then observed dosing of high dose perampanel (10mg) in the lab 1 hour before a one-time alcohol infusion . Each lab session occurs exactly a week after starting the medication for that round. The wash out period between lab test session phases will be 7-10 days. Subjects will receive 2 days of 2mg perampanel after each lab to taper down (included in the washout period). The next appointment will be brief at the start of the next phase, at which point the next week of low dose perampanel or placebo will be started. With the washout period and the 7 day taper of the next phase, the actual lab sessions will occur 14-17 days apart. All test days will involve administration of alcohol with the same 3 target doses \[target Breath Alcohol Concentration (BrAc) =20mg%, 60mg%, and 100mg%\] in a step-wise fashion.

Drug: Perampanel

Interventions

Perampanel DRUG

Perampanel is a noncompetitive (allosteric) antagonist of the AMPA-R that is well-absorbed (100% bioavailability), has good blood-brain-barrier penetration, and rapidly reaches peak plasma concentrations (1 hour). To date, there have been no clinical trials of AMPA-R antagonists (e.g., perampanel) for the treatment of alcoholism.

Also known as: AMPA-R antagonist, anticonvulsant

Perampanel 10 mg; Perampanel 6mg

Placebo DRUG

Placebo given in place of perampanel during the pre-treatment period and lab session days.

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• males and females
• between the ages of 21 and 55 years;
• Nontreatment-seeking Heavy Drinkers (NTSHDs)as defined above, and must have had at least 5 Standard Drinks (SD) in one day on at least some occasions in the past and been able to tolerate it without an adverse reaction
• generally medically and neurologically healthy on the basis of history, physical examination, Electrocardiogram, screening laboratory results (Complete Blood Count w/ differential, Thyroid Stimulating Hormone, Free-T4, Aspartate Transferase, Alanine Transferase, Gamma-Glutamyl Transferase, Blood Urea Nitrogen, creatinine, electrolytes, urinalysis, beta-Human Chorionic Gonadotropin). Individuals with Liver Function Tests (LFT) that are no more than 3 times above the normal levels will be included;
• women with a negative pregnancy test and not nursing, must be regularly using birth control
• negative breath alcohol at screening and on each test day;
• not taking any psychoactive medication or opioids (in past 30-days);
• are non-treatment seeking.

You may not qualify if:

• they need detoxification determined by a Clinical Institute Withdrawal Assessment (CIWA) score of \>8 or have had a history of alcohol detoxification in the past;
• have been in treatment for an alcohol problem within the last 6 months, or if the severity of their alcohol problem based on the research physician's assessment warrants definitive treatment;
• meet criteria for Diagnostic Statistical Manual (DSM) -IV psychiatric and substance use disorder diagnosis (other than alcohol abuse/dependence, cannabis abuse/dependence and nicotine dependence; those diagnoses will be allowed; participants can be either smokers up to 1 pack per day or non-smokers) based on history and psychiatric evaluation that includes a structured diagnostic interview (Structured Clinical Interview for DSM-IV Axis I Disorders: SCID)
• unwillingness to remain alcohol-free 12 hours prior to test days;
• have a significant ongoing serious medical condition such as Diabetes Mellitus, liver disease (see above LFT guideline), renal disease (as evidenced by serum creatinine above our laboratory's reference limit of 1.7 mg/dL, or have a history of adverse reaction to IV placement/blood draw

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• University of Connecticut: collaborator
• Yale University: collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (4)

University of Connecticut

Farmington, Connecticut, 06030, United States

Location

Yale New Haven Hospital Research Unit

New Haven, Connecticut, 06510, United States

Location

West Haven Veterans Affairs

West Haven, Connecticut, 06515, United States

Location

Albert Arias

Richmond, Virginia, 23219, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

perampanel; Anticonvulsants

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Central Nervous System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Albert Arias
• Organization: Virginia Commonwealth University

albert.arias@vcuhealth.org

8046286777

Study Officials

• Albert Arias, MD

  Virginia CommonwealthUniversity

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: April 17, 2014
• First Posted: April 22, 2014
• Study Start: June 1, 2019
• Primary Completion: February 15, 2022
• Study Completion: February 16, 2022
• Last Updated: August 18, 2023
• Results First Posted: August 18, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)