Human Laboratory Study of Apremilast for Alcohol Use Disorder

Primary: The primary objective of this study is to compare the efficacy of two different maintenance doses of apremilast (tablets) in reducing alcohol craving among subjects with moderate to severe alcohol use disorder (AUD) after two weeks of daily dosing.

Secondary: Secondary objectives include evaluation of two different maintenance doses of apremilast compared with matched placebo on other measures of self-reported alcohol consumption, alcohol craving, alcohol-related negative consequences, AUD symptoms, pain, sleep disturbances, depression, anxiety, quality of life, cigarette smoking, other nicotine use, cannabis use, retention in the study, and safety.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder; Alcohol Misuse
• Intervention / Treatment: Drug: Apremilast; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Megan Ryan, MBA; Phone Number: 3014434225; Email: mryan1@nih.gov

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California
      • Contact: Jessica Jenkins, MS; Phone Number: 310-206-6756; Email: jenkinsj@ucla.edu
      • Principal Investigator: Lara Ray, PhD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Contact: Kristen Raymond; Email: kristen.raymond@cuanschutz.edu
      • Principal Investigator: Joseph Schacht, PhD
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Recruiting
      • University of Virginia
      • Principal Investigator: Nassima Ait-Daoud Tiouririne, MD
      • Contact: Eva Jenkins-Mendoza, BS; Phone Number: 434-243-0562; Email: emj9c@hscmail.mcc.virginia.edu
      • Contact: Tracie Kostelac; Phone Number: 434.243.0563

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (not exhaustive list):

1. Be at least 21 years of age.
2. Have a current (past 12 months) DSM-5 diagnosis of AUD (4 or more symptoms) assessed using the MINI neuropsychiatric interview version 7.0.2 (at least moderate severity).
3. Have a BAC by breathalyzer equal to 0.000 when s/he signed the informed consent document (either just prior to or immediately after signing consent).
4. Be seeking treatment for problems with alcohol and express a goal of abstinence or a reduction in drinking.
5. 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.

6. Agree (if the participant is female and of childbearing potential) to use at least one of the following methods of birth control, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal:

   • oral contraceptives,
   • contraceptive sponge,
   • patch,
   • double barrier (diaphragm/spermicidal or condom/spermicidal),
   • intrauterine contraceptive system,
   • etonogestrel implant,
   • medroxyprogesterone acetate contraceptive injection,
   • complete abstinence from sexual intercourse, and/or
   • hormonal vaginal contraceptive ring.
7. Be willing to adhere to the investigational product dosing schedule.
8. Complete all assessments required at screening and baseline.
9. 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 by Study Week 6.
10. Not anticipate any significant problems with transportation arrangements or available time to travel to the study site by Study Week 6.
11. Not have any plans to move within Study Week 6 to a location which would make continued participation in the study impractical.
12. Provide contact information of someone, such as a family member, spouse, or significant other, who may be able to contact the participant in case of a missed clinic appointment.
13. Be someone who in the opinion of the investigator would be expected to complete the study protocol.
14. 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.

15. If taking a medication for depression, 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:

    • SSRIs
    • Dual uptake inhibitors
    • SNRIs
    • Tricyclic antidepressants
    • MAOIs
    • Bupropion
16. Not currently taking apremilast and agree not to take non-study supplied apremilast for the duration of the study.
17. Have normal renal function defined as creatinine clearance ≥ 60 mL per minute by the Cockcroft-Gault equation.

Exclusion Criteria:

Contact study site for exclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Apremilast 60 mg/day; Apremilast, 30mg per capsule, administered twice daily (AM/PM), Placebo, administered once daily (AM)	Drug: Apremilast; 30 mg capsule; Other Names: Otezla
Active Comparator: Oral Apremilast 90 mg/day; Apremilast, 30mg per capsule, 2 capsules (AM) and 1 capsule (PM)	Drug: Apremilast; 30 mg capsule; Other Names: Otezla
Placebo Comparator: Oral Matched Placebo; Placebo, capsule, 2 capsules (AM) and 1 capsule (PM)	Drug: Placebo; Matched Placebo Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Craving	The primary outcome measure of this study is to compare the efficacy of two different maintenance doses of apremilast (tablets) in reducing alcohol craving among participants with moderate to severe alcohol use disorder (AUD) after two weeks of daily dosing.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants with no heavy drinking days	Percentage of participants with no heavy drinking days over the last 4 weeks of the treatment period. 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 2-5
Participants abstinent from alcohol	Percentage of participants abstinent from alcohol over the last 4 weeks of the treatment period of treatment.	Weeks 2-5
Days abstinent from alcohol per week.	Percentage of days abstinent from alcohol per week.	Weeks 2-5
Participants with at least a WHO 2-level decrease in alcohol consumption	Percentage of participants with at least a WHO 2-level decrease in alcohol consumption	Weeks 2-5
Heavy drinking days per week	Percentage of heavy drinking days per week	Weeks 2-5
Participants abstinent from cigarette smoking	Percentage of participants abstinent from cigarette smoking (among smokers at baseline)	Weeks 4-5
Number of drinks per week	Mean number of drinks per consumed week	Weeks 2-5
Number of drinks per drinking day	Weekly mean number of drinks consumed per drinking day.	Weeks 2-5
Alcohol Use Disorder Symptoms	Number of Alcohol User Disorder (AUD) symptoms as measured by MINI AUD	Week 6
Number of days of cannabis use per week	Mean number of days of cannabis use per week (among cannabis users at baseline)	Weeks 4-6
Global Health Score	The PROMIS (Patient-Reported Outcomes Measurement Information System) Global Health Scale is QOL assessment to evaluate the clinical benefit of apremilast treatment. It is a 10-question self-report measure that rates items on a 5-item ordinal scale (5 = Excellent, 1 = Poor) over the past 7 days. It assesses five core health domains: physical function, pain, fatigue, emotional distress, and social health. Scores will be converted to T-scores (normalized for comparison across populations). Lower scores correspond to more severe problems. Global health score measured by the PROMIS-Global Health scale	Weeks 4,6
Alcohol Negative Consequences Score	For negative consequences for alcohol use, the short form of the PROMIS Patient-Reported Outcomes Measurement Information System) Alcohol Negative Consequences questionnaire will be used to assess outcomes of alcohol use over the past 7 days. This 7-item questionnaire assesses physical and social consequences of drinking. Scores will be converted to T-scores (normalized for comparison across populations).	Weeks 4,6
Sleep Disturbance	The PROMIS (Patient-Reported Outcomes Measurement Information System) Sleep Disturbances Scale - short form is an 8-item scale asking questions about sleep disturbances in the past 7-days. Each item on the measure is rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; and 5=always) with a range in score from 8 to 40 with higher scores indicating greater severity of sleep disturbance. Scores will be converted to T-scores (normalized for comparison across populations).	Weeks 4,6
PROMIS pain intensity score	The PROMIS (Patient-Reported Outcomes Measurement Information System) Adult Short Form version 1.0 Pain Intensity will be used to assess pain intensity using a 7-day recall period (2 items) and pain intensity right now (1 item). Each item has a 5-point scale with anchors at "had no pain" and "very severe". The responses to each item will be summed to calculate a total pain intensity score. Scores will be converted to T-scores (normalized for comparison across populations).	Weeks 4,6
PROMIS-Anxiety Scale score	The PROMIS (Patient-Reported Outcomes Measurement Information System) Anxiety Scale - short form is a 8-item scale asking questions about anxiety in the past 7 days with anchors at 1 (never) and 5 (always). Interpretation of scoring is as follows: Score 0-4: Minimal Anxiety. Score 5-9: Mild Anxiety. Score 10-14: Moderate Anxiety. Score greater than 15: Severe Anxiety. Scores will be converted to T-scores (normalized for comparison across populations).	Weeks 4-6
HAM-D17 score	A 17-item clinician administered Hamilton Depression scale (HAM-D17) will be used to monitor the development of depressive symptom throughout the study. A structed interview guide must be followed by the administrator performing this assessment. HAM-D17 scores of below 7 (no depression), 7 to 17 (mild depression), 18 to 24 (moderate depression) and 25 and above (severe depression) (Carrozzino-2020). This questionnaire will be completed by the interviewer and will be both the source and eCRF.	Weeks 2,4,6
Urge to Drink scale scores	Urge to Drink craving score during the minimum period. Minimum score of = 0 and maximum = 35	Weeks 2-5
Inflammatory Markers	Clinical chemistry and hematology laboratory tests will be performed at the clinical site's local clinical laboratory.	Weeks 3, 6

Collaborators and Investigators

• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Daniel Falk, PhD, National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: January 6, 2026
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; apremilast
• Other Study ID Numbers: HLAB-004

Drug and device information, study documents

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