Pharmacogenetic Study of Ondansetron in Alcohol Use Disorder

Inclusion Criteria

• Men and women who have given written informed consent
• Aged 18 to 70
• The subject has a breath alcohol concentration (BrAC) = 0.00% at the screening visit and or = 9 will be evaluated by the PI or designee to determine eligibility. Subjects who are deemed by the PI or designee to be at risk of suicide will be excluded.
• Clinically significant, unstable physical illness (e.g., hematologic, hepatic or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance), as judged by the PI or designee to be exclusionary
• Clinically significant abnormal vital signs, as judged by the PI or designee
• Clinically significant abnormal 12-lead ECG at the Screen 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 (average of 3 12-lead measurements)
• Serum potassium, magnesium or calcium levels outside the central laboratory's reference range that are deemed clinically significant by the PI or designee.
• Taking medications (within the last 7 days prior to the Baseline Visit) that have the potential to prolong the QT interval, as judged by a study physician, or may require such medications during the course of the study. For patients taking these medications, a study physician will evaluate the potential for ondansetron to interact with the medication to produce a clinically significant risk for the participant.
• Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia or indwelling cardiac pacemaker
• Complete left bundle branch block
• History of Long QT Syndrome or a first-degree biological family member with this condition
• Evidence of hepatic failure and/or ascites, prolonged prothrombin time (International Normalized Ratio [INR] > or = 1.7), bilirubin >10% above the upper limit of the central lab's normal range and/or esophageal variceal disease
• Active hepatitis and/or serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) or lactate dehydrogenase (LDH) > 3x the upper limit of normal
• Treatment, either current or within 28 days prior to Randomization, with any medications having a potential effect on alcohol consumption and related behaviors or mood. These include opioid antagonists (e.g., naltrexone, Vivitrol®, Selincro®), glutamate antagonists (e.g., acamprosate), anticonvulsants (e.g., topiramate, gabapentin), 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®)
• At the Screen Visit, the subject's urine contains opiates, cocaine, amphetamines, barbiturates, or benzodiazepines that cannot be explained by appropriate use of prescribed medication
• History of severe or life-threatening adverse reactions to ondansetron
• Female subjects of childbearing potential who have a positive pregnancy test at Baseline Visit or are pregnant, breast feeding, not adhering to an acceptable form of contraception at screening or any time during the study, or unwilling to maintain an acceptable form of contraception throughout the study
• Prior to Randomization, the subject is compelled to participate in an alcohol treatment program to maintain his/her liberty
• As of Screen Visit, the subject is sharing a household with a subject randomized to any investigational trial of ondansetron
• Any other condition or therapy that, in the investigator's opinion, may pose a risk to the subject, prevent the subject from completing the required study procedures or interfere with the study objectives • Less than 75% European ancestry prop