Study to Evaluate AD04 in Adults With Alcohol Use Disorder (AUD) and Selected Serotonin Transporter Polymorphisms

NCT04101227 | Completed Phase 3 DMC

• 1 other identifier: AD04-301
• Study Type: interventional
• Target: 302
• Locations: 7 countries
• Sites: 25

Brief Summary

Randomized, multi-center, double-blind, parallel-group, placebo-controlled study. Eligible subjects will be randomized to receive either 0.33 mg AD04 or placebo orally twice-daily for 24 weeks in conjunction with brief psychological counseling. Randomization will be stratified by:

1. 1.Level of alcohol consumption prior to enrollment in the study (heavy drinkers averaging \<10 drinks per day of drinking or very heavy drinkers averaging ≥10 drinks per day of drinking), and
2. 2.Gender (male or female).

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the percentage of monthly heavy drinking days (PHDD)

  Change from baseline in the percentage of monthly HDDs, where (heavy) drinking is defined as the consumption of ≥ 60 g alcohol/day (if male) or ≥ 40 g alcohol/day (if female).

  Weeks 16 to 24

Secondary Outcomes (10)

• Change from baseline in the primary efficacy endpoint at each study month

  Weeks 4, 8, 12, 16, 20, and 24

• Change from baseline in AUD symptoms and clinical status

  Weeks 12 and 24

• Change from baseline in Drinking Risk Levels (DRL), 1-level shift

  Week 24

• Change from baseline in Drinking Risk Levels (DRL), 2-level shift

  Week 24

• Change from baseline in total alcohol consumption (TAC)

  Weeks 16 to 24

Study Arms (2)

Treatment Arm

EXPERIMENTAL

AD04 (ondansetron)

Drug: AD04 (ondansetron); Device: Companion Diagnostic for Genetic Testing; Behavioral: Brief Psychological Counseling

Placebo Arm

PLACEBO COMPARATOR

Matching Placebo

Drug: Matching placebo; Device: Companion Diagnostic for Genetic Testing; Behavioral: Brief Psychological Counseling

Interventions

AD04 (ondansetron) DRUG

AD04 (ondansetron) 0.33 mg, orally (p.o.) twice a day (BID)

Treatment Arm

Matching placebo DRUG

Matching placebo to AD04 (ondansetron), orally (p.o.) twice a day (BID)

Placebo Arm

Companion Diagnostic for Genetic Testing DEVICE

Companion Diagnostic for Genetic Testing

Placebo Arm; Treatment Arm

Brief Psychological Counseling BEHAVIORAL

Brief Psychological Counseling

Placebo Arm; Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has signed the Informed Consent Form.
• The subject has breath alcohol concentration (BAC) of 0.00% at the Screening and \< 0.02 % at the Baseline visit.
• The subject has moderate to severe diagnosis of AUD as measured by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria.
• Males and females aged 18 and over.
• Able to provide Timeline Follow-back Method (TLFB) alcohol consumption information for the 28-day period prior to Screening Visit.
• A subject is eligible for participation in the study if he/she had:
• ≥6 HDDs (HDD is defined as a day with alcohol consumption of 60 g or more for males and 40 g or more for females) in the 4 weeks prior to the Baseline Visit,
• an average alcohol consumption at the medium risk level (defined by the WHO "International guide for monitoring alcohol consumption and related harm" as \>40 grams of ethanol/day for males and \>20 grams of ethanol/day for females) for the 4 weeks prior to the Screening Visit,
• ≤14 consecutive abstinent days in the 4 weeks preceding the Screening Visit.
• Willingness to provide a blood sample for DNA analysis at the Screening visit. The blood sample collected for DNA testing contains at least one of the following genotypes as measured by Adial's validated method:
• rs4795541-LL genotype of the insertion-deletion polymorphism (5'-HTTLPR) in the 5'-regulatory region and rs1042173-TT SNP in the 3'-untranslated region of SLC6A4 gene that encodes the serotonin transporter
• rs1150226-AG SNP in HTR3A, the gene that encodes subtype A of the serotonin-3 receptor
• rs1176713-GG SNP in HTR3A, the gene that encodes subtype A of the serotonin-3 receptor
• rs17614942-AC in HTR3B, the gene that encodes subtype B of the serotonin-3 receptor
• Expressed a wish to reduce or stop alcohol consumption.

You may not qualify if:

• Patients with withdrawal symptoms requiring additional medication for withdrawal. If present at Screening/Baseline Visit, subjects must complete a medically supervised detoxification program prior to being able to enroll in the study.
• Subjects with diagnosis of any of the following concomitant psychiatric disorders: non-treated, unstable schizophrenia, bipolar disorder, other psychotic disorder during the lifetime of the subject. Recent (within last 12 months) diagnosis of a major depressive disorder, post traumatic stress disorder, panic disorder or eating disorders. Subjects with nicotine use disorder, phobic or other anxiety disorders (other than post-traumatic stress disorder or panic disorder) can be included.
• The subject reports current or recent (within 8 weeks prior to Baseline Visit) treatment with antipsychotics or antidepressants medications, which can have an effect on serotonin receptor or transporter actions.
• The subject has been treated with any investigational medicinal product within 30 days or 5 half-lives (whichever is longer) prior to the Baseline Visit.
• The subject is currently participating or has recently (4 weeks prior to the Baseline Visit) participated in a treatment program for alcohol use disorders.
• Any subject who has suicidal thoughts as evaluated by the Columbia Suicide Severity Rating Scale (C-SSRS) (i.e., has any suicidal ideation of type 4 or 5 on the C-SSRS in the last month).
• The subject has a clinically significant untreated and unstable illness, for example, hepatic or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance.
• The subject has clinically significant abnormal vital signs.
• The subject has a clinically abnormal ECG at the Screening/Baseline Visit, clinically significant cardiovascular disease requiring regular or intensive clinical monitoring, a current history of arrhythmias, or a current or past history of clinically significant QT prolongation, including:
• QTcF \> 450 ms (one ECG at screening and average of 3 12-lead measurements at baseline)
• serum potassium, magnesium or calcium levels outside the central laboratory's reference range
• receiving medications (within the last 7 days prior to the Baseline Visit) that have the potential of prolonging the QT interval or may require such medications during the course of the study
• clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia or indwelling pacemaker
• complete left bundle branch block
• history of Long QT Syndrome or an immediate family member with this condition

Sponsors & Collaborators

• Adial Pharmaceuticals: lead

Study Sites (25)

Mental Health Centre Prof. Dr. Ivan Temkov Burgas EOOD Department for treatment of Emergency Psychiatric conditions

Burgas, Bulgaria

Location

State Psychiatric Hospital

Kardzhali, Bulgaria

Location

UMHAT Dr. Georgi Stranski Second Psychiatric Clinic

Pleven, Bulgaria

Location

Ambulatory for Group Practice for Specialized Psychiatric Help - Philipopolis OOD

Plovdiv, Bulgaria

Location

Medical Center Intermedica OOD

Sofia, Bulgaria

Location

State Psychiatric Hospital for Treatment of drug addiction and alcoholism

Sofia, Bulgaria

Location

Diagnostic-Consultative Center Mladost-М Varna

Varna, Bulgaria

Location

Clinical Hospital Center Split

Split, Croatia

Location

Polyclinic Neuron

Zagreb, Croatia

Location

University Psychiatric Hospital Vrapče Klinika za psihijatriju Vrapče

Zagreb, Croatia

Location

West Tallinn Central Hospital, Haabersti Health Center

Tallinn, Estonia

Location

Addiktum klinikka Helsinki

Helsinki, 00120, Finland

Location

Savon psykiatripalvelu

Kuopio, Finland

Location

Mentalcare

Oulu, Finland

Location

Satakunnan Psykiatripalvelu Oy

Pori, Finland

Location

Satakunnan Psykiatripalvelu Oy

Tampere, Finland

Location

Addiktum Oy

Turku, Finland

Location

Liepaja Regional Hospital Addictive disorder department

Liepāja, Latvia

Location

M&M Centrs

Riga, Latvia

Location

Strenci Psychoneurological Hospital

Strenči, Latvia

Location

Centrum Medyczne Luxmed Sp. z. o. o.

Lublin, Poland

Location

NZOZ Prywatna Klinika Psychiatryczna

Tuszyn, Poland

Location

Clinical Research Group Sp. z.o.o

Warsaw, Poland

Location

Ladulaas Kliniska Studier

Borås, Sweden

Location

ClinSmart Sweden AB

Uppsala, Sweden

Location

Related Links

• A Prospective Pharmacogenetic Phase 3 Clinical Trial of Low-Dose Ondansetron (A 5-HT3 Antagonist) to Treat Heavy and Very Heavy Drinkers With Alcohol Use Disorder
• Safety and compliance of long-term low-dose ondansetron in alcohol use disorder treatment

MeSH Terms

Conditions

Alcoholism

Interventions

Ondansetron; Genetic Testing

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Professor, Dr Hannu Alho

  National Institute for Health and Welfare Research Center Biomedicum

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2019
• First Posted: September 24, 2019
• Study Start: February 1, 2020
• Primary Completion: February 18, 2022
• Study Completion: March 18, 2022
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CR (3); LA (3); BU (7); FI (6); PL (3); SE (2); ES (1)