A clinical study to evaluate the efficacy, safety and tolerability of AD04 (ondansetron) in adults with alcohol use disorder (AUD) and certain genetic characteristics
- Conditions
- Adult patients diagnosed with moderate or severe alcohol use disorderMedDRA version: 20.1Level: PTClassification code 10080021Term: Alcohol use disorderSystem Organ Class: 10037175 - Psychiatric disordersTherapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2019-000737-39-LV
- Lead Sponsor
- Adial Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 290
1. The subject has signed the Informed Consent Form.
2. The subject has breath alcohol concentration (BAC) of 0.00% at the Screening and < 0.02 % at the Baseline visit.
3. The subject has moderate to severe diagnosis of AUD as measured by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria.
4. Males and females aged 18 and over.
5. Able to provide Timeline Follow-back Method (TLFB) alcohol consumption information for the 28-day period prior to Screening Visit.
6. A subject is eligible for participation in the study if he/she had:
a. =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,
b. 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,
c. =14 consecutive abstinent days in the 4 weeks preceding the Screening Visit.
7. 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
8. Expressed a wish to reduce or stop alcohol consumption.
9. Willingness to participate in behavioral and medicinal treatments for AUD.
10. Has had a stable residence in the 28 days prior to the Baseline Visit in the study and has no plans to move in the next 9 months. A stable residence is a domicile in which an individual can operate as if it were his or her own homestead and does not include shelters or halfway houses.
11. Able to read and understand, and complete the rating scales and questionnaires accurately, follow instructions, and make use of the behavioral treatments.
12. The subject, if female must:
• have a negative urine pregnancy test prior to the initiation of treatment and agree not to try to become pregnant during the study
• use an adequate method of contraception [intrauterine device, oral contraceptives, progesterone implanted rods, or regular medroxyprogesterone acetate injections or double barrier method (condom or diaphragm + spermicide)], or
• be post-menopausal having had the last natural menstruation at least 24 months prior to the Screening Visit, or
• have had a hysterectomy or been surgically sterilized prior to baseline.
13. The subject if male and has a female partner of childbearing potential, must use a condom as a contraceptive method up to the safety follow-up visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90
1. 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.
2. 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-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.
3. 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.
4. 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.
5. The subject is currently participating or has recently (4 weeks prior to the Baseline Visit) participated in a treatment program for alcohol use disorders.
6. Any subject who has suicidal thoughts as evaluated by the Columbia Suicide Severity Rating Scale (C-SSRS).
7. 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.
8. The subject has clinically significant abnormal vital signs.
9. 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.
10. Serum potassium, magnesium or calcium levels that are below or >10% above the central laboratory's reference range, If serum potassium, magnesium, or calcium is below lower normal range, subject is allowed to take a supplement and be re-assessed before baseline.
11. The subject with elevated liver function tests or diagnosis of hepatic failure, esophageal variceal disease or any other clinically significant hepatic disease.
12. The subject reports treatment, either current or within 28 days prior to the Baseline Visit, with any medications having a potential effect on alcohol consumption and related behaviors or mood. These include opiate antagonists (e.g., naltrexone, Vivitrol®, Selincro®), glutamate antagonists (e.g., acamprosate), anticonvulsants (e.g., topiramate), serotonin reuptake inhibitors (e.g., fluoxetine), serotonin antagonists (e.g., buspirone), other antidepressants (e.g., tricyclic antidepressants or monoamine oxidase inhibitors), dopamine antagonists (e.g. haloperidol), and disulfiram (Antabuse®). Note benzodiazepines are allowed if used chronically.
13. The subject reports treatment at Baseline with any of the prohibited medications.
14. Previous or current abuse of benzodiazepines.
15. The subject has a history of allergic reactions or other known intolerance to ondansetron or other 5-HT3 antagonists.
16. Female subjects of childbearing potential who have a positive pregnancy test at Screening/Baseline Visit or are pregnant, breast feeding and who are unwilling to adhere to an acceptable form of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method