NCT05554926

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

A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [4-14C] AEF0117 Following a Single Oral Dose in Healthy Male Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Aelis Farma · Industry
• Sex: Male
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

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.

Detailed description

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. The safety and tolerability of AE0117 has been demonstrated in the clinical studies conducted to date. The purpose of this study is to determine the absorption, metabolism, and excretion of \[4 14C\]AEF0117 and to characterize and determine the metabolites present in plasma, urine, and, where possible, feces in healthy male subjects following a single oral administration. Knowledge of the metabolism and excretion of parent drug and its metabolites is useful for evaluating the Metabolites in Safety Testing requirements elucidated in the Food and Drug Administration (FDA) Guidance and International Conference on Harmonisation (ICH) M3 and the likelihood of effects of renal or hepatic impairment on the disposition of AEF0117 and the likelihood for drug-drug interactions with AEF0117. 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. 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. If the following criteria are not met by Day 28, subjects will continue study participation and will be asked to return for a residential visit on Day 35 to allow for continuation of the 24-hour collection (urine, blood, and feces) for total radioactivity: * plasma radioactivity levels below the limit of quantitation for 2 consecutive collections, * ≥90% mass balance recovery, and * ≤1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 2 consecutive 24-hour periods. If the following criteria are not met at the Day 35 visit, then the subjects will be required to come back on Day 42 to allow for continuation of the 24-hour collection (urine, blood, and feces) for total radioactivity: * plasma radioactivity levels below the limit of quantitation for 2 consecutivecollections, and * ≤1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 24-hour period. Subjects will be discharged from the study at the latest discharge day of Day 43, unlessotherwise agreed upon by the sponsor and investigator. Up to 8 subjects will be enrolled to ensure that 6 subjects complete the study.

Conditions

• Marijuana Abuse

Interventions

Type	Name	Description
DRUG	AEF0117	2 mg AEF0117 containing approximately 100 μCi of \[4-14C\]AEF0117

Timeline

• Start date: 2022-12-16
• Primary completion: 2023-02-24
• Completion: 2023-02-24
• First posted: 2022-09-26
• Last updated: 2023-04-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study