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.


Eligibility Criteria:
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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