A Phase I Study of the Interaction of Alcohol With Oral AFA-281 in Healthy Volunteers

• Adults between 21 and 55 years of age, inclusive.
• Must voluntarily sign and date each informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.
• Currently consumes alcohol regularly (defined as having consumed 7 to 21 standard drinks per week on average in the 6 months prior to screening and having consumed ≥5 standard drinks on at least one occasion in the 30 days prior to screening) but does not meet the DSM-5 criteria for Alcohol Use Disorder. Note: one standard alcoholic drink is equivalent to 1.5 oz. hard liquor or 5 oz. wine or 12 oz. beer.
• Body mass index (BMI) within the range of 18.5 to 30.0 kg/m2, inclusive.
• A condition of general good health, based upon the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG) at the screening visit
• Adequate venous access
• Must be surgically sterile (vasectomy, tubal ligation or hysterectomy) or agree to be sexually inactive or agree to use a barrier method of birth control (i.e., condom) from the start of screening until study completion, and agree to refrain from donating sperm, for 90 days after study drug administration.
• Agree to abstain from strenuous exercise during the inpatient stay of the study.

Exclusion Criteria:

• History of significant sensitivity to any drug.
• Has a clinically significant abnormal ECG or an ECG with a QTc interval corrected for heart rate using the Fridericia formula (QTcF) > 430 msec.
• Has an estimated creatinine clearance (CrCl) outside of normal range.
• History of head trauma with loss of consciousness, seizures or convulsions, including febrile, alcohol or drug withdrawal seizures.
• History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption.
• Requirement for any over-the-counter and/or prescription medication, vitamins and/or herbal supplements on a regular basis.
• Use of any medications, vitamins and/or herbal supplements within the 2-week period prior to study drug administration.
• Positive test result for hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) or HIV antibodies (HIV Ab). Negative HIV status will be confirmed at Screening and the results will be maintained confidentially by the study site.
• Display any latent signs of alcohol withdrawal per the Clinical Institute Withdrawal of Alcohol Assessment-Revised (CIWA-AR).
• History or current diagnosis of a substance use disorder.
• Positive urine drug screen for drugs of abuse at Screening or Day -1.
• Consumption of alcohol within the 1-day period prior to study drug administration.
• Receipt of any drug by injection within 30 days prior to study drug administration.
• History of epilepsy, any clinically significant cardiac, respiratory (except mild asthma), renal, hepatic, gastrointestinal, hematologic, endocrine, dermatological, metabolic or psychiatric disease or disorder, or any uncontrolled medical illness.
• A clinically notable vital sign abnormality including a history of syncopal or near syncopal events following abrupt change in posture.
• History of cardiac disease, including family history of long-QT syndrome, second degree heart block Type II, third degree heart block or unexplained sudden deaths in their family.
• Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt of a transfusion of any blood product within 8 weeks prior to study drug administration.
• Pregnant or nursing women
• Receipt of any investigational product within 6 weeks prior to study drug administration.
• Consumption of grapefruit or grapefruit products from 3 days prior to study drug administration.
• Use of tobacco or nicotine-containing products within the 6-month period preceding study drug administration.
• Current enrollment in another clinical study.
• Previous enrollment in this study.
• Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive AFA-281.