Medication Development in Alcoholism: Apremilast Versus Placebo

Medication Development for Protracted Abstinence in Alcoholism: Apremilast Versus Placebo

The primary hypotheses under test are that alcohol dependent subjects treated with apremilast 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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • The Scripps Research Institute Pearson Center for Alcoholism and Addiction Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female volunteers, 18-65 years of age
• Meets 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 BAC and a CIWA score of < 9 at time of 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.
• Females with childbearing potential must have a negative pregnancy test on the screening, randomization, and lab session 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 procedure
• Willing to comply with the provisions of the protocol and take daily oral medication.

Exclusion Criteria:

• Active suicidal ideation, as systematically assessed with the Columbia Suicide Severity Rating Scale.
• Meets DSM-5 criteria for a major psychiatric disorder, including mood or anxiety disorders or substance use disorders other than alcohol or nicotine
• Has a urine drug screen (UDS) positive for substances of abuse other than alcohol.
• Significant medical disorders that will increase potential risk or interfere with study participation as determined by the study physician
• Known hypersensitivity to apremilast
• 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], anticonvulsants, or antidepressants).
• 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 required by a specific protocol.
• 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: Apremilast (Otezla); Fixed oral dose of 90 mg/d following the standard titration for a total dosing duration of 14 days.	Drug: Apremilast; Fixed oral dose of 90 mg/d following the standard titration for a total dosing duration of 14 days.; Other Names: Otezla
Placebo Comparator: Placebo; Identical placebo pills taken orally for 14 days	Drug: Placebo; Identical placebo pills taken orally for 14 days; Other Names: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Craving to Drink	Total Visual Analog Scale (VAS) scores of craving severity in response to in vivo alcohol cues. Higher scores indicate greater craving severity with a minimum score of 0 and a maximum score of 80.	1 hour on the last day of dosing (Day 14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drinking	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. Treatment effects on drinking were accessed during the 11 days of ad libidum and did not include the final three days of mandatory abstinence prior to cue reactivity testing on day 14 of dosing.	11 days (Treatment effects on drinking were accessed during the 11 days of ad libidum and did not include the final three days of mandatory abstinence prior to cue reactivity testing on day 14 of dosing.)

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 1, 2017
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 2, 2017
• First Posted (Actual): June 5, 2017

Study Record Updates

• Last Update Posted (Actual): September 16, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

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; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: U01AA025476 (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.: No