Human Laboratory Study of ASP8062 for Alcohol Use Disorder

The primary objective of this study is to evaluate the effects of ASP8062, 25 mg once a day and matched placebo, on alcohol cue-elicited alcohol craving during a human laboratory paradigm after 2 weeks of daily dosing among subjects with moderate to severe alcohol use disorder (AUD) as confirmed by the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5™). Secondary objectives include evaluation of ASP8062, 25 mg once a day, and matched placebo on reduction of alcohol consumption, alcohol craving, cigarette smoking (among smokers), mood, sleep, alcohol use negative consequences, study retention, and safety and tolerability throughout the last 4 weeks of the treatment phase of the study.

Study Overview

• Status: Completed
• Conditions: Alcohol Drinking; Alcohol Use Disorder; Alcohol Use Disorder (AUD)
• Intervention / Treatment: Drug: ASP8062; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Brown University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Be at least 21 years of age.
2. Meet the DSM-5 criteria for AUD of at least moderate severity.
3. Be seeking treatment for AUD and desire a reduction or cessation of drinking.
4. Be able to verbalize an understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English and able to complete the questionnaires required by the protocol.

5. Agree (if the subject is female and of child bearing potential) to use at least one of the following methods of birth control to at least 30 days post the last dose of study drug, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal (one year):

   1. oral contraceptives,
   2. contraceptive sponge,
   3. patch,
   4. double barrier (diaphragm/spermicidal or condom/spermicidal),
   5. intrauterine contraceptive system,
   6. etonogestrel implant,
   7. medroxyprogesterone acetate contraceptive injection,
   8. true abstinence: when this is in line with the preferred and usual lifestyle of the participant,
   9. and/or hormonal vaginal contraceptive ring.
6. Agree (if female) to not donate ova for at least 30 days following the last ASP8062 administration.

7. Agree (if male) to use acceptable methods of contraception if the male participant's partner could become pregnant from the time of the first administration of the study drug until 90 days following the final administration of the study drug. One of the following acceptable methods of contraception must be utilized:

   1. surgical sterilization (vasectomy);
   2. the participant's female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or sub dermal implants (commenced at least 14 days prior to study drug administration to the male participant)
   3. the participant's female partner uses a medically prescribed topically applied transdermal contraceptive patch (commenced at least 14 days prior to study drug administration to the male participant);
   4. the participant's female partner has undergone tubal ligation (female sterilization) or is postmenopausal (one year);
   5. the participant's female partner has undergone placement of an intrauterine device or intrauterine system; and,
   6. true abstinence: when this is in line with the preferred and usual lifestyle of the participant.
8. Agree (if male) to refrain from sperm donation from the randomization visit to at least 90 days after the last dose of study drug.
9. Be able to take oral medication and be willing to adhere to the medication regimen.
10. Complete all assessments required at screening and baseline.

11. Have a place to live in the 2 weeks prior to randomization and not be at risk that s/he will lose his/her housing in the next 2 months.

    Not anticipate any significant problems with transportation arrangements or available time to travel to the study site over the next 2 months.

12. Not have any unresolved legal problems that could jeopardize continuation or completion of the study.
13. Provide contact information of someone, such as a family member, spouse, or significant other, who may be able to contact the subject in case of a missed clinic appointment.
14. Have a BAC by breathalyzer equal to 0.000 when s/he signed the informed consent document.

15. If taking a medication for depression or anxiety, must have been taking a stable dose in the 2-months prior to randomization and plan to continue during the study. This includes drugs such as the following:

    1. Selective serotonin reuptake inhibitors (SSRIs)
    2. Dual uptake inhibitors
    3. Serotonin-norepinephrine reuptake inhibitors (SNRIs)
    4. Tricyclic antidepressants
16. Be someone who in the opinion of the investigator would be expected to complete the study protocol.
17. Agree to the schedule of visits, verbally acknowledge that s/he will be able to attend each scheduled visit, participate in phone visits and that s/he does not have any already scheduled events or a job that may substantially interfere with study participation.
18. Be willing to use a smartphone's video capability to record daily oral ingestion of tablets for the entire 6-week treatment period (subject's own smartphone or one provided by AiCure).

19. Have sitting (3 to 5 minutes) vital signs at the screening visit within the following limits:

    1. Systolic blood pressure 90 to 140 mmHg
    2. Diastolic blood pressure of 50 to 90 mmHg
    3. Heart rate of 40 to 90 beats per minute

Exclusion Criteria:

1. Current (past 12 months) substance use disorder of at least moderate severity (4 or more criteria) for any psychoactive substance other than alcohol and nicotine, including sedatives and hypnotics, or cocaine use disorder of any severity as defined by DSM-5 criteria.
2. Be mandated by the court to obtain treatment for alcohol-dependence, or has probation or parole requirements that might interfere with study participation.
3. Be anyone who in the opinion of the investigator could not be safely withdrawn from alcohol without medical detoxification.

4. Have any of the following, based on DSM-5 criteria as assessed using theMINI:

   1. Current or lifetime diagnosis of psychotic disorders,
   2. Current bipolar disorder,
   3. Current major depressive episode,
   4. Current (past 3 months) eating disorder (anorexia or bulimia), or
   5. Within past year diagnosis of panic disorder with or without agoraphobia.

Contact site for additional exclusion criteria.

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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: Matching Placebo	Drug: Placebo; 1 x per day for 6 weeks
Experimental: ASP8062 (25 mg once daily)	Drug: ASP8062; ASP8062 is a novel compound with positive allosteric modulator (PAM) activity on the γ-aminobutyric acid type B (GABAB) receptor, 25 mg, 1 x per day for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Craving	Strength of alcohol craving Visual Analogue Scale (VAS) score; min=0, max=20; higher scores = more craving (worse outcome)	Week 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With no Heavy Drinking Days	Number of subjects that have no heavy drinking days during weeks 3 to 6 of the treatment phase. A "heavy drinking day" is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men.	Weeks 3 to 6 of the treatment phase
Number of Subjects Abstinent From Alcohol	Number of subjects that have not drank alcohol during Weeks 3 to 6 of the treatment phase.	Weeks 3 to 6 of the treatment phase
WHO 1-level Decrease in Alcohol Consumption	The number of subjects experiencing at least a 1-level decrease in World Health Organization (WHO) levels of alcohol consumption from the level at baseline (the period including the 28 days before screening) to the level during Weeks 3 to 6 of the treatment phase. The WHO levels of average alcohol consumption per day 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 where 14g = 1 SDU (WHO-2000). In computing the WHO alcohol consumption level, average drinks per day were used, computed as the sum of all drinks in the 28 day period divided by the number of days with non-missing drinking data in that period. Abstinent subjects were included in a separate "Abstinent" category.	Weeks 3 to 6 of the treatment phase
WHO 2-level Decrease in Alcohol Consumption	The number of subjects experiencing at least a 2-level decrease in World Health Organization (WHO) levels of alcohol consumption from the level at baseline (the period including the 28 days before screening) to the level during Weeks 3 to 6 of the treatment phase. The WHO levels of average alcohol consumption per day 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 where 14g = 1 SDU (WHO-2000). In computing the WHO alcohol consumption level, average drinks per day were used, computed as the sum of all drinks in the 28 day period divided by the number of days with non-missing drinking data in that period. Abstinent subjects were included in a separate "Abstinent" category.	Weeks 3 to 6 of the treatment phase.
Percentage of Days Abstinent	The percentage of days abstinent from drinking alcohol	Weeks 3 to 6 of the treatment phase
Percentage of Heavy Drinking Days	Percentage of heavy drinking days where a heavy drinking day is 4 or more drinks on a day for women or 5 or more drinks on a day for men.	Weeks 3 to 6 of the treatment phase
Drinks Per Week	The number of drinks consumed per week	Weeks 3 to 6 of the treatment phase
Drinks Per Drinking Day	The number of drinks consumed on days where participants drank	Weeks 3 to 6 of the treatment phase
Penn Alcohol Craving Scale (PACS)	The amount of craving; higher numbers indicate more craving. There are 5 items each on a 0 to 6 scale. Items are summed to get to the total craving, resulting in scores having a min=0 and max=30.	Weeks 3 to 6 during the treatment phase, averaged
Pittsburgh Sleep Quality Index (PSQI)	A measure of sleep quality; the PSQI includes a scoring key for calculating a patient's seven subscores, each of which can range from 0 to 3. The subscores are tallied, yielding a "global" score that can range from 0 to 21. A global score of 5 or more indicates poor sleep quality; the higher the score, the worse the quality.	Weeks 4 & 6 of the treatment phase, averaged
Patient-Reported Outcomes Measurement Information System (PROMIS) Alcohol Related Negative Consequences	A measure of alcohol-related negative consequences. There are 7 items scored on a 1 to 7 scale (a higher score indicative greater frequency of negative consequences). The items are summed and converted to a T-score to create a total score. The T-scores range from 0 to 100 (the population mean = 50 and standard deviation = 10). Higher T-scores are indicative of more negative consequences (worse outcome).	Week 6 of the treatment phase
Profile of Mood States (POMS) Total Disturbance	A measure of total mood disturbance. Total mood disturbance is the sum of depression, anger, fatigue, confusion, and tension subscales subtracting the vigor subscale items. The range of possible scores is from -32 to 200 with higher scores indicating greater mood disturbance.	Weeks 4 & 6 of the treatment phase, averaged
Cigarettes Smoked Per Day (Among Smokers)	The number of cigarettes smoked per day, computed among individuals who smoked at baseline	Weeks 3 to 6 of the treatment phase

Collaborators and Investigators

• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Collaborators: Astellas Pharma Inc
• Investigators: Study Director: Raye Litten, Ph.D., National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Actual): March 22, 2023
• Study Completion (Actual): March 22, 2023

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: October 19, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Alcoholism; Alcohol Drinking; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Analgesics; Neurotransmitter Agents; GABA Modulators; GABA Agents; ASP8062
• Other Study ID Numbers: HLAB-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data and supporting information will be shared with the general research community upon request.
• IPD Sharing Time Frame: Data will be available approximately 6/25/2025 for an indefinite time period
• IPD Sharing Access Criteria: Data users will be encouraged to complete a Data Use Agreement and obtain authorization for data use by the NIAAA Data Access Committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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