Study of [4-14C] AEF0117 Following a Single Oral Dose in Healthy Male Subjects

NCT05554926 | Completed Phase 1 FDA Drug

• 1 other identifier: AEF0117-106
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Cannabis use is increasing and will only further escalate with legalization of recreational and medical cannabis use in western countries , with a prevalence greater than 30 % in the US and most European countries for individuals between 16 and 24 years of age. Approximately 9 % of those who use cannabis will become addicted. The number goes up to about 1 in 6 among those who start using cannabis as teenagers and to 25 to 50 % among those who smoke cannabis daily. The consequences of cannabis abuse in the most prone population (14-25 years of age) are extremely serious, and may include addiction, altered brain development, poorer educational outcomes, cognitive impairment, lower income, greater welfare dependence, unemployment and lower relationship and life satisfaction. There are no available pharmacological treatments of cannabis use disorder (CUD). Thus, the development of safe and effective medications for the treatment of CUD is an urgent public health priority. The preclinical efficacy and available ADMET (Administration, Distribution, Metabolism, Elimination and Toxicology) in animal and human data suggest that AEF0117, an investigational new study drug, could constitute a very efficacious and safe treatment for cannabis abuse disorders. The purpose of this research is to study how AEF0117 influences the subjective effects of cannabis in subjects with CUD. AEF0117 acts in the same parts of the brain as THC (tetrahydrocannabinol), the active ingredient of marijuana, and may temporarily alter some of cannabis's effects. This will be a Phase 1, open-label, nonrandomized, single-dose study in healthy male subjects. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the dose administration. Subjects will be admitted into the study site on Day 1. On the morning of Day 1, all subjects will receive a single oral dose of 2 mg containing approximately 100 μCi of \[4-14C\]AEF0117 approximately 1 hour after completion of a low fat breakfast.

Conditions

Marijuana Abuse

Keywords

AEF0117

Outcome Measures

Primary Outcomes (7)

• Urine excretion of [4-14C]AEF0117

  Fraction excreted (Fe) based on urine collection

  Up to 648 hours post dose

• Feces excretion of [4-14C]AEF0117

  Fraction excreted (Fe) based on feces collection

  Up to 648 hours post dose

• Area under the concentration-time curveof AEF0117

  Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration;(AUC0-t) based on serial blood sample collections and plasma AEF0117 concentration

  Up to 432 hours postdose

• Maximum observed concentration;of AEF0117

  Peak Plasma Concentration (Cmax) induced by a single dose of AEF0117 will be determined based on serial blood sample collections and plasma AEF0117 concentration.

  Up to 432 hours postdose

• Time of the maximum observed concentration;of AEF0117

  Time to maximum plasma concentration (tmax) of a single dose of AEF0117 will be determined based on serial blood sample collections and plasma AEF0117 concentration.

  Up to 432 hours postdose

• Apparent terminal elimination half-lifeof AEF0117

  Apparent terminal elimination half-life (t1/2); based on serial blood sample collections and plasma AEF0117 concentration.

  Up to 432 hours postdose

• Total radioactivity

  Measure of total radioactivity in plasma and whole blood

  Up to 1008 hours postdose

Secondary Outcomes (4)

• Identification of potential metabolites

  Up to 984 hours postdose

• Incidence of treatment-emergent AEs and SAEs as assessed by vital signs

  24 hours from dosing

• Incidence of treatment-emergent AEs and SAEs as assessed by ECGs

  24 hours from dosing

• Incidence of laboratory abnormalities

  Up to 672 hours postdose

Study Arms (1)

[4-14C] AEF0117

EXPERIMENTAL

Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the dose administration. Up to 8 subjects will be enrolled to ensure that 6 subjects complete the study. Subjects will be admitted into the study site on Day -1. On the morning of Day 1, all subjects will receive a single oral dose of 2 mg containing approximately 100 μCi of \[4-14C\]AEF0117 approximately 1 hour after completion of a low-fat breakfast

Drug: AEF0117

Interventions

AEF0117 DRUG

2 mg AEF0117 containing approximately 100 μCi of \[4-14C\]AEF0117

Also known as: 3ß-(4-methoxybenzykoxy)pregn-5-en-20-one t)

[4-14C] AEF0117

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Female subjects will be excluded to align with regulatory guidance. The 'as low as (is) reasonably achievable' (ALARA) principle prescribed by the FDA for the US recommends that radiation exposure to subjects should be kept ALARA; therefore, if no specific reason exists to include females (ie, no available data suggest metabolism of the AEF0117 is different in females versus males), then the radiation exposure to female subjects should ideally be kept at 0 by not including females in this radioactivity study and only enrolling and dosing male subjects.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males, of any race, between 18 and 65 years of age, inclusive, at screening.
• Body mass index between 18.0 and 30.0 kg/m2, inclusive.
• In good health, determined by no clinically significant findings from medical history,12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check-in and from the physical examination at check-in, as assessed by the investigator (or designee).
• Males will agree to use contraception
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
• History of a minimum of one bowel movement per day.

You may not qualify if:

• Medical conditions
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
• History of significant hypersensitivity, intolerance, or allergy to corn products/oil, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed). Cholecystectomy is not allowed.
• Confirmed vital signs measurements below:
• systolic blood pressure \>140 or \<90 mmHg, systolic blood pressure \>160 or \<90 mmHg for male volunteers between 60 and 65 years old
• diastolic blood pressure \>90 or \<50 mmHg, and
• pulse rate \>100 or \<40 beats per minute. Minor deviations from the normal range may be allowed if deemed by the investigator to have no clinical significance, after discussion with medical monitor.
• Positive hepatitis panel and/or reactive human immunodeficiency virus test
• Positive coronavirus disease 2019 (COVID-19) test less than 30 days prior to screening and/or experiencing symptoms.
• Prior/concomitant therapy
• Administration of a COVID-19 vaccine in the past 30 days prior to dosing.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, and/or use or intend to use any drugs known to induce or inhibit CYP isozymes, within 30 days prior to check-in, unless deemed acceptable by the investigator (or designee) and accepted by sponsor's medical monitor.
• Use or intend to use any prescription medications/products within 14 days prior to check-in, and any medication with an elimination half-life of \>60 hours (time since last dose of at least 6 times the elimination half-life), unless deemed acceptable by the investigator (or designee) and with consultation with sponsor's medical monitor.
• Use or intend to use slow-release medications/products considered to still be activewithin 14 days prior to check-in, unless deemed acceptable by the investigator (or designee) and accepted by sponsor's medical monitor.

Sponsors & Collaborators

• Aelis Farma: lead

Study Sites (1)

Labcorp Clinical Research Unit Inc.

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Marijuana Abuse

Condition Hierarchy (Ancestors)

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

Study Officials

• Irene Mirkin, MD

  Substance Use Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to 8 subjects will be enrolled to ensure that 6 subjects complete the study. Subjects will be admitted into the study site on Day -1. On the morning of Day 1, all subjects will receive a single oral dose of 2 mg containing approximately 100 μCi of \[4-14C\]AEF0117 approximately 1 hour after completion of a low-fat breakfast. Subjects will reside at the study site from Day -1 through Day 28 and will be discharged on Day 28

Study Record Dates

• First Submitted: September 22, 2022
• First Posted: September 26, 2022
• Study Start: December 16, 2022
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: April 7, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)