Bioequivalence Assessment of Cannabidiol (CBD) Administrated in Oral Formulations

Pain Clinical Trial

Official title: Bioequivalence Assessment of Cannabidiol (CBD) Administrated in Oral Formulations

Status Recruiting

Clinical Trial Summary

The oral bio-availability of cannabidiol (CBD) is low due to poor water solubility and susceptibility to extensive first pass metabolism, resulting in relative bio-availability of 6%.This project is designed to evaluate the plasma concentration vs. time profile of a self emulsifying drug delivery system termed Long Chain Nano Lipospheres (LNL) for enhancing the oral bio-availability of cannabidiol (CBD). The main goal of this study is to evaluate the bio-equivalence of CBD in the LNL product, compared to CBD in a sesame oil vehicle and CBD without any formulation, in powder form. Bio-equivalence is measured by AUC 0-24h, Tmax and Cmax.

Clinical Trial Description

Cannabidiol (CBD) is considered the non-psychoactive component of the cannabis plant with a myriad of pharmacological attributes. There is preliminary data that CBD can be a useful treatment for different therapeutic conditions such as epilepsy, anxiety, pain etc. CBD has been investigated for its analgesic effect in patients with neuropathic and chronic pain, especially resistant to other treatments. Further supportive evidence for CBD's efficacy in treatment of pain, is established pre-clinically and requires additional research in a clinical setting. The use of CBD in epilepsy has been assimilated in treatment guidelines in many countries including Israel. However, the potential medical use of whole-plant cannabis extracts, particularly in children with a developing brain, is limited by the psychoactive properties and the adverse effects associated with long-term THC use. Although a therapeutic rational for the use of CBD has been demonstrated, an optimal oral dosage form to deliver this compound is not available yet. Oral administration is challenging because of CBD's poor solubility and extensive first pass metabolism, leading to an oral bioavailability of approximately 6%. In this project, investigators utilize a bio-pharmaceutical method to enhance the bioavailability of CBD using an advanced self-emulsifying drug delivery system termed Long Chain Nano Lipospheres (LNL). The LNL formulation is composed of long chain triglycerides, surfactants and co-solvent. This constellation is termed the pre-concentrate, which dissolves CBD in its lipid core and administered in a soft gelatin capsule. When reaching the aqueous phase of the GI tract, this pre-concentrate spontaneously forms a drug encapsulated O/W nano emulsion. Previously, investigators have shown in a pre-clinical investigation that incorporation of CBD into the LNL is a promising strategy to increase the compound's bioavailability. The primary goal of this study is to evaluate the bioequivalence of the developed CBD-LNL product to CBD in a sesame oil vehicle and CBD in powder form. Sesame oil is the commonly used vehicle for cannabinoids oral uptake for lack of other options. However, this option often leads to significant inter and intra subject variability in cannabinoids' plasma concentrations. The study will be performed on 12 healthy male volunteers. It will be randomized, blind, three way cross-over study intended to evaluate the pharmacokinetics of CBD. Each volunteer will receive CBD-LNL capsule, CBD in sesame oil vehicle capsule and CBD without any vehicle in powder form. All study groups will receive the same dose of CBD-90 mg. Blood samples will be drawn from forearm 30 minutes before (pre-dose) and every 30 minutes interval for the first 4 hours, then samples will be taken at 5,6,7,8,12 and 24 hours after the intake of the study drug. Blood concentration profiles of CBD and its main metabolites 7-hydroxy-CBD and CBD-glucoronide-11 will be determined in order to calculate the pharmacokinetic parameters of CBD. ;

Related Conditions & MeSH terms

• Pain

• NCT number: NCT03877991
• Study type: Interventional
• Source: Hadassah Medical Organization
• Contact: Elyad Davidson, MD
• Phone: +972507874098
• Email: EDAVIDSON@hadassah.org.il
• Status: Recruiting
• Phase: Early Phase 1
• Start date: February 19, 2024
• Completion date: February 19, 2025