Medication Development in Alcoholism: Suvorexant Versus Placebo

Medication Development for Protracted Abstinence in Alcoholism: Suvorexant Versus Placebo

The primary hypotheses under test are that alcohol dependent subjects treated with suvorexant will report decreased craving for alcohol following alcohol exposure in the laboratory and report significantly less drinking under naturalistic conditions, than those treated with placebo. Suvorexant (Belsomra®) received approval by the FDA in 2014 for treatment of insomnia. To control for any effect of pre-existing sleep disturbance for which suvorexant may be indicated, subjects will be stratified on the basis of a Pittsburgh Sleep Quality Index total score of > 5 versus <5. Subjects were also stratified by sex.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder (AUD)
• Intervention / Treatment: Drug: Suvorexant 20 mg; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037-4657
      • Scripps Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female volunteers, 18-65 years of age.
• Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for current alcohol use disorder of moderate or greater severity (AUD-MS).
• In the month prior to screening, reports drinking ≥ 21 standard drinks per week if male, ≥ 14 if female, with at least one heavy drinking day (≥ 5 males, ≥ 4 females) per week.
• Subjects will not be seeking treatment because the medication studies are not treatment trials, and to avoid exposing treatment-seekers to alcohol cues
• Subjects must be abstinent a minimum of 3 days (but not more than 7 days) prior to the human lab session.
• Negative blood alcohol content (BAC) and a Clinical Institute Withdrawal Assessment (CIWA) score of < 9 at time of randomization and lab session to eliminate acute alcohol or withdrawal effects on dependent measures.
• In acceptable health in the judgment of the study physician, on the basis of interview, medical history, physical exam, EKG, routine urine and blood chemistry.
• Subjects with a history of depression, who have been on a stable dose of anti-depressant medication for at least 3 months, and do not meet current DSM-5 criteria for depression or anxiety.
• Females with childbearing potential must have a negative pregnancy test on the screening and randomization visits and agree to use effective birth control for the duration required by a given study.
• Able to provide informed consent and understand questionnaires and study procedures in English.
• Willing to comply with the provisions of the protocol and take oral medication.

Exclusion Criteria:

• Meets DSM-5 criteria for a major psychiatric disorder, including mood or anxiety disorders or substance use disorders other than alcohol or nicotine, or, mild cannabis use disorder
• Has a urine drug screen (UDS) positive for substances of abuse other than alcohol or marijuana
• Significant medical disorders that will increase potential risk or interfere with study participation as determined by the study physician.
• Liver function tests more than 3 times the upper limit of normal or elevated bilirubin.
• Subjects taking digoxin or CYP3A inhibitors or inducers, metabolism by CYP3A is the major elimination pathway for suvorexant.
• Treatment within the month prior to screening with (1) an investigational drug, (2) medications which may negatively interact with study medications, or (3) drugs that may influence study outcomes (e.g., disulfiram [Antabuse], naltrexone [ReVia], acamprosate [Campral], or anticonvulsants).
• Ongoing treatment with medications that may increase risk, including prescribed, over-the-counter, and herbal preparations, as determined by the study physician.
• Sexually active female subjects with childbearing potential who are pregnant, nursing, or refuse to use effective methods of birth control for the duration of the study.
• No fixed domicile and/or no availability by home or mobile telephone.
• History of hypersensitivity to the study drug or the ingredients.
• Failure to take double-blind medication as prescribed.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Belsomra,(suvorexant); 20 mg single-dose administration given on an inpatient clinical research unit	Drug: Suvorexant 20 mg; Single-dose administration of 20 mg suvorexant given on an inpatient clinical research unit; Other Names: Belsomra
Placebo Comparator: Placebo; Placebo single-dose administration given on an inpatient clinical research unit	Drug: Placebo oral tablet; Single-dose administration of placebo given on an inpatient clinical research unit; Other Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale (VAS) of Craving Severity: 2 Arms	VAS to alcohol cues minus VAS to water cues on a 0-20 VAS scale. Higher scores indicate greater craving strength with a minimum score of 0 and a maximum score of 20.	1 hour during cue reactivity session
Visual Analog Scale (VAS) Strength of Craving: Combined Arms Conditional Model	VAS to alcohol cues minus VAS to water cues on a 0-20 VAS scale. Higher scores indicate greater craving strength with a minimum score of 0 and a maximum score of 20.	1 hour during cue reactivity session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Standard Drinks Per Day: 2 Arms	Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcohol drinks consumed per day with a minimum value of 0 and an undetermined maximum value	Up to one week following single dose administration
Number of Standard Drinks Per Day: Combined Arms Conditional Model	Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcoholic drinks consumed per day with a minimum value of 0 and an undetermined maximum value.	Up to one week following single dose administration

Collaborators and Investigators

• Sponsor: The Scripps Research Institute
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2021
• Primary Completion (Actual): November 8, 2022
• Study Completion (Actual): November 8, 2022

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 13, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: P60AA006420 (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
• product manufactured in and exported from the U.S.: Yes