The Effect of Food on the Oral Bioavailability of AEF0117 in Healthy Volunteers

Marijuana Abuse Clinical Trial

Official title: The Effect of Food on the Oral Bioavailability of AEF0117 in Healthy Volunteers

Status Active, not recruiting

Clinical Trial 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. 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.

In the 3 early studies conducted with AEF0117, AEF0117 was administered orally after a light breakfast. AEF0117 showed a good bioavailability and favorable, dose-proportional pharmacokinetics . In this protocol, the effects of food on AEF0117 bioavailability in healthy volunteers will be investigated by comparing the rate and extent of AEF0117 when 1 mg AEF0117 is administered in fed state versus fasting state.

The safety and tolerability of AE0117 has been demonstrated in the clinical studies conducted to date. This trial will provide data on the effect of food on the oral bioavailability of AEF0117 to support the next stage of the clinical development of the drug.

Clinical Trial Description

Cannabis is the most widely used illicit drug with approximately 28 million individuals reporting past-month use, and 14% of those receiving substance use disorder treatment in the US reporting cannabis as their primary drug of abuse. While psychotherapeutic approaches have some utility for treating Cannabis Use Disorder (CUD), the vast majority of patients have difficulty significantly reducing their use or achieving abstinence. Safe and effective medications to treat CUD are urgently needed. The overall goal of this clinical trial is to contribute to advancing a safe and effective pharmacotherapy for CUD along the FDA approval pipeline.

When the CB1 receptors are over-activated by very high doses of THC, quite higher than the doses of THC used by cannabis abusers, the concentration of the steroid hormone pregnenolone increases in the brain. Pregnenolone then binds to a specific site on the CB1 receptors, distinct for the one of CB1 agonists and THC, and acts as an endogenous signaling specific inhibitor of the CB1 receptors. Pregnenolone cannot be used as a pharmacological treatment because it is poorly bioavailable, has a very short half-life and is converted downstream to active steroids. Aelis Farma, in collaboration with researchers from the Institut National de la Santé et de la Recherche Médicale (INSERM), has developed a new pharmacological class, the synthetic signaling specific inhibitor of the CB1 receptor (sCB1-SSi) AEF0117, by modifying pregnenolone's chemical structure to prevent conversion to active steroids, and to increase absorption and biological stability while maintaining THC antagonism.

To date, 3 clinical studies have been completed with AEF0117 including 2 phase 1 studies in healthy volunteers (AEF0117-101 single ascending dose study and AEF0117 102, multiple ascending dose study), and a phase 2a trial in cannabis users (AEF0117 201). The phase 1 studies showed good safety and tolerability of AEF0117 in the dose range tested (0.2 mg as single dose and 0.6-6 mg/day as single and multiple doses) and the phase 2a trial found that the 1 mg/day dose of AEF0117 significantly reduced both the abuse-related subjective effects of cannabis and its self-administration, while the 0.06 mg dose did not. Importantly, AEF0117 was well tolerated in daily cannabis smokers, with no evidence of precipitated withdrawal, physical, or psychological discomfort. There were no SAEs and a limited number of TEAEs. These results confirm preclinical data showing that AEF0117 does not function as an orthosteric antagonist and does not produce any of the adverse effects associated with rimonabant. Thus, AEF0117 is to our knowledge the first medication to safely and robustly attenuate the positive subjective and reinforcing effects of cannabis in participants with CUD.

In the 3 early studies conducted with AEF0117, AEF0117 was administered orally after a light breakfast. AEF0117 showed a good bioavailability and favorable, dose-proportional pharmacokinetics . In this protocol, the effects of food on AEF0117 bioavailability in healthy volunteers will be investigated by comparing the rate and extent of AEF0117 when 1 mg AEF0117 is administered in fed state versus fasting state.

The safety and tolerability of AE0117 has been demonstrated in the clinical studies conducted to date. This trial will provide data on the effect of food on the oral bioavailability of AEF0117 to support the next stage of the clinical development of the drug. ;

Related Conditions & MeSH terms

• Marijuana Abuse

• NCT number: NCT05451017
• Study type: Interventional
• Source: Aelis Farma
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 4, 2023
• Completion date: June 2024