Investigation of the Pharmacokinetic Profile of CBD

The goal of the current study is to evaluate the bioavaibiltiy of CBD in normal healthy Individuals. This is an open cross-over design study in healthy individuals to assess the safety and pharmacokinetic (PK) effects of cannabidiol.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Cannabidiol; Drug: Cannabidiol; Drug: Cannabidiol

Detailed Description

The goal of this study is to determine the pharmacokinetics and pharmacodynamic profile of CBD in normal healthy individuals under standard and high fat fed conditions.

CBD has recently gained significant attention as a potential treatment for various disorders. One aspect for consideration in the development of CBD medication in capsule form is the poor bioavailability of cannabinoids such as CBD to obtain clinically effective doses since only ~4-6% of CBD is absorbed orally. This study will investigate the potential of CBD in a formulation in a capsule to enhance bioavailability, reduce the incidence of gastrointestinal side effects, reduce first pass metabolism and enhance onset time. This PK study will be conducted with standard meal and high fat conditions in normal healthy volunteers in a cross-over design, separated by a washout period of 1 week. Healthy volunteers are defined as having no significant health-related issues (i.e., the absence of significant medical, psychosocial, or emotional conditions) that are verified by clinical and psychiatric assessments.

The study will first evaluate in healthy volunteers the PK, tolerability and safety profiles of a new CBD formulation designed to improve bioavailability.

Test conditions and order:

1. 200 mg CBD (standard meal)
2. 400 mg CBD (standard meal)
3. 400 mg Epidiolex (standard meal)
4. 400 mg CBD (high fat meal)

Blood samples will be taken at -60,15, 30, 45 and 60 min and 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours associated with administration of the CBD capsules.

Monitoring period for PK: 24 hours (plasma and urine PK). Participation in 4 test conditions for a duration of approximately 4 weeks and a 1 week follow-up assessment. Total length of in-house stay is 12 hours, with participants returning the following day for 24 hour time point procedures.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to understand and give informed consent;
2. Individuals between 18 and 65 years old; Sex is used a biological factor (50% of individuals recruited will be females, allowing sex comparisons).
3. English speakers.
4. Being healthy as determined by study physician according to screening medical and psychiatric history, physical examination, vitals, ECG and safety laboratory values. Only healthy volunteers with normal hepatic laboratory values will be enrolled.
5. Healthy volunteers who are medication- and drug-free, including free from nicotine and any prescribed medications.

Exclusion Criteria:

1. Having present or past medical conditions, including a DSM-5 Axis I psychiatric disorder, history of cardiac disease, arrhythmias, neurological disease of central origin, head trauma, and seizures
2. Using any psychoactive drug (other than nicotine) in at least the past 7 days (determined by lack of acute-opioid or other drugs related withdrawal symptoms and the negative result of a urine drug screen including an opioid drug metabolite test, and alcohol breathalyzer to detect alcohol intoxication);
3. Positive urine drug screen (cocaine, opiates, benzodiazepines, barbiturates, amphetamines, morphine, methadone, methamphetamines, oxycodone, phencyclidine, tricyclic antidepressant, tetrahydrocannabinol, buprenorphine, methylenedioxymethamphetamine, propoxyphene);
4. Having a history of hypersensitivity to cannabinoids or any of the ingredients in the product (gelatin and/or sesame oil);
5. Being pregnant or breastfeeding;
6. Not using an appropriate method of contraception such as hormonal contraception (oral hormonal contraceptives, Depo-Provera, Nuva-Ring), intrauterine device (IUD), sterilization, or double barrier method (combination of any two barrier methods used simultaneously, i.e. condom, spermicide, diaphragm);
7. Participating in another pharmacotherapeutic trial in the past 3 months;
8. History of impaired renal function or elevated liver enzymes at prescreening. The exclusionary lab values are: 3x nl AST/ALT, 1.5x bilirubin or 50% reduction in eGFR.
9. Participants who have used any medication, dietary supplements (and/or grape fruit juice), or combination of medications and supplements known to alter the metabolism of, or interact with CBD (bupropion, rifampin, barbiturates, phenothiazines, cimetidine, etc.) 14 days prior to and during the duration of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test condition 1; Cannabidiol 200 mg with standard meal	Drug: Cannabidiol; Cannabidiol 200 mg; Other Names: Nantheia ATL5; Drug: Cannabidiol; Cannabidiol 400 mg; Other Names: Nantheia ATL5; Drug: Cannabidiol; Epidiolex 400 mg; Other Names: Epidiolex
Experimental: Test condition 2; Cannabidiol 400 mg with standard meal	Drug: Cannabidiol; Cannabidiol 200 mg; Other Names: Nantheia ATL5; Drug: Cannabidiol; Cannabidiol 400 mg; Other Names: Nantheia ATL5; Drug: Cannabidiol; Epidiolex 400 mg; Other Names: Epidiolex
Experimental: Test condition 3; Epidiolex 400 mg with standard meal	Drug: Cannabidiol; Cannabidiol 200 mg; Other Names: Nantheia ATL5; Drug: Cannabidiol; Cannabidiol 400 mg; Other Names: Nantheia ATL5; Drug: Cannabidiol; Epidiolex 400 mg; Other Names: Epidiolex
Experimental: Test condition 4; Cannabidiol 400 mg with high fat meal	Drug: Cannabidiol; Cannabidiol 200 mg; Other Names: Nantheia ATL5; Drug: Cannabidiol; Cannabidiol 400 mg; Other Names: Nantheia ATL5; Drug: Cannabidiol; Epidiolex 400 mg; Other Names: Epidiolex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and adverse effects	Safety and adverse effects will be assessed with the Systematic Assessment for Treatment Emergent Events (SAFTEE).	Study Visit 1 Day
Area under the plasma concentration curve (AUC)	Area under the plasma concentration versus time curve	Time point -60,15, 30, 45 and 60 minutes and 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours associated with administration of the CBD capsules.
Peak plasma concentration (Cmax)	Peak plasma concentration of CBD and its metabolites	Time point -60,15, 30, 45 and 60 minutes and 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours associated with administration of the CBD capsules.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the urine concentration curve (AUC)	Area under the urine concentration versus time curve	Time point -60 minutes and 2, 4, 6, 8, 10, 12, 24 hours associated with administration of the CBD capsules.
Peak urine concentration of CBD (Umax)	Peak urinary excretion of CBD and its metabolites	Time point -60 minutes and 2, 4, 6, 8, 10, 12, 24 hours associated with administration of the CBD capsules.

Collaborators and Investigators

• Sponsor: Hurd,Yasmin, Ph.D.
• Investigators: Principal Investigator: Yasmin Hurd, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2021
• Primary Completion (Actual): February 14, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 27, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Cannabidiol; Epidiolex
• Additional Relevant MeSH Terms: Anticonvulsants; Cannabidiol
• Other Study ID Numbers: IRB-19-02132

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No