Bioequivalence Assessment of Cannabidiol (CBD) Administrated in Oral Formulations
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03877991|
Recruitment Status : Not yet recruiting
First Posted : March 18, 2019
Last Update Posted : March 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Pain||Drug: CBD-sesame oil capsule Drug: CBD-LNL capsule Drug: CBD powder form capsule||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||randomized blind, three way cross-over study|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||Bioequivalence Assessment of Cannabidiol (CBD) Administrated in Oral Formulations|
|Estimated Study Start Date :||April 2019|
|Estimated Primary Completion Date :||August 2019|
|Estimated Study Completion Date :||August 2019|
Experimental: CBD-sesame oil capsule
12 volunteers will receive a single oral dose of CBD in a sesame oil vehicle filled in a capsule, with 200 mL of water. The dose of CBD to be administrated is 90 mg.
Drug: CBD-sesame oil capsule
A capsule containing cannabidiol dissolved in sesame oil and surfactant vehicle.
Other Name: Cannabidiol in sesame oil vehicle cpausle
Experimental: CBD-LNL capsule
12 volunteers will receive a single oral dose of CBD-LNL formulation filled in a capsule, with 200 mL of water. The dose of CBD to be administrated is 90 mg.
Drug: CBD-LNL capsule
A capsule containing Cannabidiol dissolved in self nano emulsifying formulation
Other Name: Cannabidiol in Long Chain Nano Lipospheres formulation
Experimental: CBD powder form capsule
12 volunteers will receive a single oral dose of CBD in powder form filled in a hard gelatin capsule, with 200 mL of water. The dose of CBD to be administrated is 90 mg.
Drug: CBD powder form capsule
Powder of Cannabidiol filled in a hard gelatin capsule, without formulation.
Other Name: Cannabidiol solid dosage form
- Pharmacokinetic parameters of CBD [ Time Frame: 1 year ]Assesment of the pharmacokinetic profile of Cannabidiol in healthy volunteers. Plasma concentrations will be determined using HPLC-MS/MS validiated assay. The unit of measure will be provided as ng/ml.
- Exposure to the metabolites of the study drugs [ Time Frame: 1 year ]Assessment of the metabolic profile of the major cannabidiol metabolites: 7-hydroxy-CBD and CBD-glucoronide-11 in healthy volunteers. Plasma metabolites concentrations will be determined using HPLC-MS/MS validiated assay. The unit of measure will be provided as ng/ml.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03877991
|Contact: Elyad Davidson, MD||+972507874098||EDAVIDSON@hadassah.org.il|
|Contact: Dvora Izgelovfirstname.lastname@example.org|
|Hadassah Medical Organization||Not yet recruiting|
|Jerusalem, Israel, 9112001|
|Contact: Hadas Lemberg, PhD +97226777572 email@example.com|
|Principal Investigator: Elyad Davidson, MD|
|Principal Investigator:||Elyad Davidson, MD||Hadassah Medical Organization|