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

NCT06719908 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AFA-281-303
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate if alcohol interacts with the drug candidate AFA-281 in adults (healthy volunteers). This trial will evaluate blood concentration levels of AFA-281 and ethanol. The main questions it aims to answer are: Does alcohol interact with AFA-281? What are the side effects (if any)? Researchers will compare AFA-281 to a placebo (a look-alike substance that contains no drug) to see if AFA-281 interacts with alcohol. Participants will take a total of 4 treatment sessions separated by at least 2 days between treatments. The treatments will incorporate AFA-281 or placebo with ethanol or ethanol placebo. After each treatment vital signs will be monitored and blood collected to measure AFA-281 and ethanol levels. Participants will provide an assessment survey of symptoms. The total treatment time will be 9 inpatient days (8 nights), and a final follow-up visit 3 to 5 days after clinic discharge.

Conditions

Alcohol; Alcohol Use Disorders

Keywords

AFA-281; Alcohol; Ethanol; Healthy Volunteer

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetic evaluation of AFA-281

  Evaluation of AFA-281 concentrations in the blood over time

  Predose and 1, 2, 2.25, 2.5, 2.75, 3, 3.25, 4, 5, 6, 7, 8, 12 and 24 hours post dose

• Evaluation of ethanol levels in the blood

  Measure ethanol concentrations in the blood over time

  Collected at 2, 2.25, 2.5, 2.75, 3, 3.25, 4, 5, 6, 7, 8, 12 and 24 hours post administration

• Dizziness visual analog scale (VAS) assessment

  Central nervous system test. Visual Analogue Scale for dizziness assessment on a scale 0 to 10. 0 no dizziness and 10 worst

  Collected at predose, 1, 2, 3, 4, 6 and 8 hours post dose

• Choice Reaction Time (CRT) evaluation

  Central nervous system test. The subject is required to respond to one stimulus, the quicker the better

  Predose and 1, 2, 3, 4, 6 and 8 hours post dose

• Balance Platform assessment

  Central nervous system test. Balance platform assessment

  Predose and 1, 2, 3, 4, 6 and 8 hours post dose

• Match to Sample Visual Search (MTS) assessments

  Central nervous system test. Assesses attention and visual searching, with a speed accuracy trade-off. The quicker, the better.

  1, 2, 4 and 8 hours post dose

• Alertness visual analog scale (AVAS)

  Central nervous system test. Asks a subject to indicate their feelings on a line with a scale from 0 mm on the left to 100 mm on the right. The scale can be used to assess sleepiness and other subjective experiences.

  1, 2, 4 and 8 hours post dose

Secondary Outcomes (6)

• Clinical chemistry

  Baseline, pre-intervention and in 24 hours after completion of the intervention

• A complete blood count (CBC) with differential

  Baseline, pre-intervention and in 24 hours after completion of the intervention

• Heart Rate

  Predose, 1, 2, 4 hours post dose

• Blood pressure, both systolic, and diastolic pressure

  Predose, 1, 2, 4 hours post dose

• Body weight

  Baseline, pre-intervention and after in 24 hours of the intervention

Study Arms (4)

AFA-281 with Ethanol

ACTIVE COMPARATOR

AFA-281 (40 mg) will be administered as a single dose (oral) in combination with Alcohol (0.6 g/kg in females or 0.7g/kg in males).

Drug: AFA-281 is a small molecule, orally available; Other: Alcohol (Ethanol)

AFA-281 with Ethanol Placebo

PLACEBO COMPARATOR

AFA-281 (40 mg) will be administered as a single dose (oral) in combination with the Alcohol placebo (0.6 g/kg in females or 0.7g/kg in males).

Drug: AFA-281 is a small molecule, orally available

AFA-281 placebo with Ethanol

PLACEBO COMPARATOR

AFA-281 placebo (40 mg) will be administered as a single dose (oral) in combination with the Alcohol (0.6 g/kg in females or 0.7g/kg in males).

Other: Alcohol (Ethanol)

AFA-281 placebo with Ethanol placebo

SHAM COMPARATOR

AFA-281 placebo (40 mg) will be administered as a single dose (oral) in combination with the Alcohol placebo (0.6 g/kg in females or 0.7g/kg in males).

Drug: AFA-281 is a small molecule, orally available; Other: Alcohol (Ethanol)

Interventions

AFA-281 is a small molecule, orally available DRUG

This is a study to evaluate the interaction of AFA-281 with alcohol

AFA-281 placebo with Ethanol placebo; AFA-281 with Ethanol; AFA-281 with Ethanol Placebo

Alcohol (Ethanol) OTHER

Alcohol will be administered in combination with AFA-281 or AFA-281 placebo

AFA-281 placebo with Ethanol; AFA-281 placebo with Ethanol placebo; AFA-281 with Ethanol

Eligibility Criteria

• Age: 21 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Afasci Inc: lead

MeSH Terms

Conditions

Alcoholism

Interventions

Ethanol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Central Study Contacts

Simon Xie, MD

CONTACT

650-995-7320; simonxie@afasci.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2024
• First Posted: December 6, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2029
• Last Updated: December 6, 2024

Record last verified: 2024-11