CBD Pharmacokinetics, Healthy Participants
Conditions
Keywords
Cannabidiol, Pharmacokinetic, Safety
Brief summary
Cannabidiol (CBD), derived from the Cannabis sativa plant, is being investigated for its potential health benefit without the psychoactive properties and adverse reactions that arise from the use of delta-9-tetrahydrocannabinol (Δ9-THC). Few studies have characterized the pharmacokinetic (PK) effects and safety of oral CBD administration. Epidiolex (Epidyolex), an oil form of CBD, is the only marketed monotherapy approved by the United States Food and Drug Administration (FDA) and Health Canada. Delivery of a CBD in a powder/capsule form may provide a more efficient method for consumers. The goal of this study is to characterize the PK profile of the test product, CBD-NE (a capsule formulation) compared to Epidyolex under both fasted and fed conditions. Each participant will receive a dose of each product under both fed and fasted conditions in a crossover design.
Detailed description
CBD and Δ9-THC are the most abundant extracts from the Cannabis sativa plant. Δ9-THC is typically associated with psychotropic effects due to its affinity for cannabinoid receptor types 1 and 2. CBD possesses a low affinity and lack of function at these receptors; therefore there is an interest in its potential health benefit without the psychoactive properties and adverse reactions that arise from Δ9-THC use. Only few studies have characterized the PK effects and the safety of oral CBD administration. As CBD is a lipophilic molecule, consuming CBD with a lipid formulation may increase its exposure. Additionally, CBD is known to have poor bioavailability when taken orally because it is rapidly metabolized by the liver to 7-hydroxycannabidiol (7-OH-CBD) and then to cannbidiol-7-oic acid (7-COOH-CBD), which may reduce the potency of CBD. Formulation strategies for orally consumed CBD products are being investigated to by-pass one or both of these limitations and improve the bioavailability of CBD. Epidyolex, a purified form of CBD, is delivered in a solution of sesame oil which aids absorption. Epidyolex, marketed and sold in the US and Canada as Epidiolex, is currently the only marketed CBD monotherapy with US FDA and Health Canada approval and is approved for treatment of certain types of epilepsy. However, administration of CBD in oil form is not ideal for consumers as it is not always convenient or precise. Delivery of CBD in a powder/capsule form may provide a more efficient method of CBD consumption. The test product will be CBD-NE, a novel formulation of CBD in a powder form. This product will be investigated in healthy adults as its PK profile is not yet characterized in humans. This study is designed to be a randomized, crossover, comparator control trial to evaluate the PK profile and safety of CBD-NE compared to Epidyolex in healthy adults under both fed and fasted conditions. Two study products, CBD-NE and Epidyolex, will be administered under both fed and fasted conditions. Participants will be randomized in a 1:1:1:1 ratio to one of 4 treatment sequences. There will be a total of 4 treatment periods consisting of 2 consecutive days, and one washout period. Each dose will be followed by a minimum 14-day, maximum of 28-day washout period, with the last dose followed by a follow-up phone call which will occur within the timeframe of the longest washout period over the study. For the fed state, participants will consume a high-fat, high-calorie breakfast within the 30 minutes prior to dosing. Pharmacokinetic blood sampling will occur pre-dose and at 0.25 h, 0.5 h, 0.75 h, 1.0 h, 1.5 h, 2.0 h, 3.0 h, 4.0 h, 5.0 h, 6.0 h, 8.0 h, 12.0 h and 24.0 h post-dose. Blood samples collected will be used to assess the PK profiles of CBD-NE and Epidyolex. PK parameters measured will include maximum concentration in plasma (Cmax), time to reach maximum concentration (Tmax), elimination half-life (T1/2), area under the plasma concentration-time curve over 24 hours (AUC0-24), area under the plasma concentration-time curve from zero to infinity (AUCinf) and AUC0-24/AUCinf for CBD, 7-OH-CBD and 7-COOH-CBD. Safety endpoints will be assessed throughout the study and will include reports of adverse events, 12-lead ECG, vital signs, safety laboratory assessments, and abbreviated physical exam.
Interventions
DRUGCannabidiol (CBD) Powder
66.68 mg CBD per capsule for a total of 400 mg CBD per serving
100 mg CBD/mL for a total of 400 mg CBD per serving
Sponsors
Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
DSM Nutritional Products, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Randomized, Open-Label, Crossover
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or female participants who are 19 to 55 years of age (inclusive). 2. Have a body mass index (BMI) range of 18.0 - 29.9 kg/m2 (inclusive) and body weight ≥ 50 kg. 3. In good general health as deemed by the investigator. 4. Naïve to oral or inhaled cannabis or hemp, or light user of oral or inhaled cannabis or hemp products (not more than 2 times per month on average) who have used cannabis for recreational (non-therapeutic) purposes without severe side effects. 5. Non-smoker (including nicotine vaping) and have not used any nicotine products (e.g., patches, gums, etc.) for \>3 months prior to the first PK blood draw (Visit 2). Note: A non-smoker is defined as someone who does not habitually/regularly use products containing nicotine. 6. Have suitable veins for repeated venipuncture. 7. Have systolic blood pressure within 90 to 139 mmHg (inclusive) and diastolic blood pressure within 60 to 89 mmHg (inclusive) at screening and Visit 2. 8. Able to consume oil formulation, and swallow pills or capsules whole, and without chewing. 9. Agree to follow the restrictions on concomitant treatments listed in the protocol. 10. Agree to follow the restrictions on lifestyle listed in the protocol. 11. Agree to adhere to the contraception requirements for this study. 12. Able to consume the entire high-fat, high-calorie breakfast provided within 30 minutes at the site during Visits 2 and 4. 13. Agree to fast overnight, i.e., no food or liquids (except for water, permitted up to 1 h prior to dosing) for a minimum 10 h prior to starting the high-fat, high-calorie breakfast on Visits 2 and 4 or prior to dosing on Visits 6 and 8. 14. Have maintained consistent dietary habits (including supplement intake) and lifestyle for the last 3 months prior to screening. 15. Willing and able to agree to the requirements and restrictions of this study, be willing to voluntarily consent, and carry out all study related procedures.
Exclusion criteria
1. Participants who are lactating, pregnant, or planning to become pregnant during the study as confirmed by a positive pregnancy test during study visits or not willing to perform a pregnancy test. 2. Male participants that are planning to conceive during the study. 3. Have a known sensitivity, intolerability, or allergy to any of the study products or their excipients, or any of the items that could be included in the standardized meals/snacks. 4. Current COVID-19 infection at the time of screening or Visit 2, or currently have the post COVID-19 condition as defined by the World Health Organization (WHO) (i.e., individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by alternative diagnosis). 5. Presence of any clinically significant or abnormal results from laboratory tests at screening (Visit 1) and/or vital sign assessments at Visits 1 or 2 as judged by the investigator and or/designee. 6. Demonstrates a positive screen for Hepatitis B Surface Antigen (HBsAg), Hepatitis C (HCV), or Human Immune Deficiency Virus (HIV) at screening. 7. Demonstrates a positive urine drug screen, positive cotinine test or positive breath alcohol test at screening or Visit 2. 8. Have abnormal 12-lead electrocardiogram (ECG) results at screening or Visit 2 as determined at the discretion of the investigator. 9. Evidence of hepatic or renal dysfunction as evidenced by alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) or gamma-glutamyl transferase (GGT) being ≥ 2 times the upper limit of normal or serum creatinine value ≥ 176.84 µmol/L at screening. 10. Have thyroid disease, Type I or Type II diabetes. 11. Have a history of blood clotting disorders. 12. Have a history of heart disease/cardiovascular disease, renal or hepatic impairment/ disease, bipolar disorder, immune disorders and/or immunocompromised \[(e.g., HIV/acquired immunodeficiency syndrome (AIDS)\]. 13. Have a history of cancer (except localized skin cancer without metastases or in situ cervical cancer) within 5 years prior to the screening visit. 14. Have an abnormality or obstruction of the gastrointestinal tract precluding swallowing (e.g., dysphagia) and digestion (e.g., known intestinal malabsorption, celiac disease, inflammatory bowel disease, chronic pancreatitis, steatorrhea). 15. Have medical condition(s) known to interfere with absorption, distribution, metabolism or excretion of the study product (e.g., Crohn's disease, short bowel, acute or chronic pancreatitis or pancreatic insufficiency). 16. Major surgery with general anesthesia in the 3 months prior to screening or planned major surgery during the study. 17. Reports a significant blood loss or blood donation totaling between 101 mL to 449 mL of blood within 30 days prior to the first PK visit (Visit 2) or a blood donation of more than 450 mL within 56 days prior to Visit 2. 18. Reports donating plasma (e.g., plasmapheresis) within 15 days prior to Visit 2. 19. History of alcohol or substance abuse in the 12 months prior to screening (including having been hospitalized for such in an in-patient or out-patient intervention program). 20. Currently consumes, on average, more than 2 standard alcoholic beverages a day or has any habit of alcohol use that, to the opinion of the investigator, may be of a concern for the study. A standard alcoholic beverage is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of liquor. 21. Receipt or use of test product(s) in another research study within 28 days prior to Visit 2 or longer if the previous test product is deemed by the investigator to have lasting effects that might influence the eligibility criteria or outcomes of current study. 22. Any other medical condition/situation or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to complete the study or its measures or pose a significant risk to the participant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Properties of CBD-NE compared to Epidyolex under Fed Conditions | 0-24 hours | Area under the plasma concentration-time curve over 24 hours (AUC0-24) for CBD |
| PK Properties of CBD-NE compared to Epidyolex under Fasted Conditions | 0-24 hours | AUC0-24 for CBD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Properties of CBD-NE compared to Epidyolex under Fed Conditions | 0-24 hours | Maximum concentration in plasma (Cmax) for CBD, 7-OH-CBD and 7-COOH-CBD |
| PK Properties of CBD-NE compared to Epidiolex under Fed Conditions | 0-24 hours | AUC0-24 for 7-hydroxycannabidiol (7-OH-CBD) and cannabidiol-7-oic acid (7-COOH-CBD) |
| Total Drug Exposure of CBD-NE compared to Epidyolex under Fasted Conditions | 0-24 hours | Sum of AUC0-24 of CBD, 7-OH-CBD and 7-COOH-CBD |
| Total Drug Exposure of CBD-NE compared to Epidyolex under Fed Conditions | 0-24 hours | Sum of AUC0-24 of CBD, 7-OH-CBD and 7-COOH-CBD |
| PK Properties of CBD-NE compared to Epidyolex under Fasted Conditions | 0-24 hours | AUC0-24 for 7-OH-CBD and 7-COOH-CBD |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum Estimated Glomerular Filtration | 12 hours | Change from pre-dose in serum estimated glomerular filtration rate (mL/min/1.73\^2) |
| Serum Total Protein | 12 hours | Change from pre-dose in serum total protein (g/dL) |
| Serum Albumin | 12 hours | Change from pre-dose in serum albumin (g/dL) |
| Serum Globulin | 12 hours | Change from pre-dose in serum globulin (g/dL) |
| Serum Total Bilirubin | 12 hours | Change from pre-dose in serum total bilirubin (mg/dL) |
| Serum Glucose | 12 hours | Change from pre-dose in serum glucose concentration (mg/dL) |
| Serum Alanine Transaminase | 12 hours | Change from pre-dose in serum alanine transaminase concentration (U/L) |
| Serum Aspartate Transaminase | 12 hours | Change from pre-dose in serum aspartate transaminase concentration (U/L) |
| Serum Alkaline Phosphatase | 12 hours | Change from pre-dose in serum alkaline phosphatase concentration (U/L) |
| Whole Blood Mean Corpuscular Hemoglobin Concentration | 12 hours | Change from pre-dose in whole blood mean corpuscular hemoglobin concentration (g/dL) |
| Serum Sodium | 12 hours | Change from pre-dose in serum sodium (mmol/L) |
| Serum Potassium | 12 hours | Change from pre-dose in serum potassium (mmol/L) |
| Serum Chloride | 12 hours | Change from pre-dose in serum chloride (mmol/L) |
| Serum Urea | 12 hours | Change from pre-dose in serum urea (mg/dL) |
| Whole Blood Monocytes | 12 hours | Change from pre-dose in whole blood monocytes (cells/uL) |
| Serum Creatinine | 12 hours | Change from pre-dose in serum creatinine (umol/L) |
| Comparison of PK Properties of CBD-NE under Fed and Fasted Conditions | 0-24 hours | AUC0-24 for CBD, 7-OH-CBD and 7-COOH-CBD |
| Comparison of PK Properties of Epidyolex under Fed and Fasted Conditions | 0-24 hours | AUC0-24 for CBD, 7-OH-CBD and 7-COOH-CBD |
| Comparison of Total Drug Exposure of CBD-NE under Fed and Fasted Conditions | 0-24 hours | Sum of AUC0-24 of CBD, 7-OH-CBD and 7-COOH-CBD |
| Comparison of Total Drug Exposure of Epidyolex under Fed and Fasted Conditions | 0-24 hours | Sum of AUC0-24 of CBD, 7-OH-CBD and 7-COOH-CBD |
| Assessment of 12-lead electrocardiogram (ECG) | 12 hours | Change from pre-dose to 12 h in QRS interval as assessed by 12-lead ECG |
| Heart rate | 0-24 hours | Change from pre-dose to post-dose in heart rate (beats per minute) |
| Blood pressure | 0-24 hours | Change from pre-dose to post-dose in systolic and diastolic blood pressure (mm Hg) |
| Whole Blood Mean Platelet Volume | 12 hours | Change from pre-dose in whole blood mean platelet volume (fL) |
| Body Temperature | 0-24 hours | Change from pre-dose to 24 h in body temperature (°C) |
| Composite Measure of Physical Abnormalities Observed in A Comprehensive Physical Exam | 12 hours | Presence or absence of physical abnormalities in general appearance |
| Composite Measure of Physical Abnormalities Observed in a Comprehensive Physical Exam | 12 hours | Presence or absence of physical abnormalities of ears |
| Incidence of Adverse Events | minimum of 14 days, maximum of 28 days | Number of participants with adverse events |
| Whole Blood Hemoglobin | 12 hours | Change from pre-dose in whole blood hemoglobin (g/dL) |
| Whole Blood Hematocrit | 12 hours | Change from pre-dose in whole blood hematocrit (%) |
| Whole Blood White Blood Cells | 12 hours | Change from pre-dose in whole blood white blood cells (x10\^3/uL) |
| Whole Blood Neutrophils | 12 hours | Change from pre-dose in whole blood neutrophils (cells/uL) |
| Whole Blood Eosinophils | 12 hours | Change from pre-dose in whole blood eosinophils (cells/uL) |
| Whole Blood Basophils | 12 hours | Change from pre-dose in whole blood basophils (cells/uL) |
| Whole Blood Lymphocytes | 12 hours | Change from pre-dose in whole blood lymphocytes (cells/uL) |
| Respiratory rate | 0-24 hours | Change from pre-dose to 24 h in respiratory rate (breaths per minute) |
| Whole Blood Platelet Count | 12 hours | Change from pre-dose in whole blood platelet count (x10\^9/L) |
| Whole Blood Red Blood Cell Count | 12 hours | Change from pre-dose in whole blood red blood cell count (x10\^6/uL) |
| Gamma Glutamyl Transferase | 12 hours | Change from pre-dose in serum gamma glutamyl transferase concentration (U/L) |
| Whole Blood Red Blood Cell Distribution Width | 12 hours | Change from pre-dose in whole blood red blood cell distribution width (%) |
| Whole Blood Mean Corpuscular Volume | 12 hours | Change from pre-dose in whole blood mean corpuscular volume (fL) |
| Whole Blood Mean Corpuscular Hemoglobin | 12 hours | Change from pre-dose in whole blood mean corpuscular hemoglobin (pg) |
Countries
Canada
Outcome results
None listed