Clinical trial NCT06574100: Relative Bioavailability of Two Orally Administered CBD Formulations in Healthy Male Adults
Official title: Relative Bioavailability of Two Orally Administered CBD Formulations in Healthy Male Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pharmacokinetics
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
Collaborators: name: University of Regina
First posted: 2024-08-27
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: We plan this study as a single-site (potentially multi-site), randomized, two-arm study, with one arm being a two-sequence crossover, single buccal, or oral dose in fasted healthy male adults, and the second arm being a two-sequence cross-over, single high oral dose PK study in fasted vs fed-state healthy male adults. Participants will be randomized into four groups (n = 16 in Arm 1, 8 per group (2 groups), all males; n = 4 in Arm 2, 2 per group (2 groups) all males) (ages 18 - 35) based on which formulation each group will receive. Individuals in study arm 1 will complete the study in the fasted state (10 hours of fasting). Individuals in study arm 2 will follow the fed-state protocol as outlined by the United States FDA's bioequivalent studies guideline
Primary purpose: BASIC_SCIENCE

Brief summary: This project is aimed at understanding whether a new fast-dissolving cheek-administered cannabidiol strip will be absorbed better into the body than cannabidiol powder. The results of this study will help guide dosage formulation choices as well as dosing regimens in NFL athletes for concussion management.

Detailed description: Cannabis formulations are typically administered by the oral route of administration. This route represents the most common administration route for most pharmaceuticals due to the ease of administration and convenience. Inhalational products are not acceptable for the sport's athlete population due to potential damage to lung tissues. Topical products do not have adequate bioavailability to meet our therapeutic objectives. Our PK studies, then, need to employ the same dosage form and route of administration we expect to use in future clinical efficacy trials.

Given the low bioavailability expected with CBD oral formulations, we wish to assess two different formulations and the relative extent of CBD absorption. Our future planned CBD intervention studies in athletes will require use of larger doses of CBD. The formulation with the larger bioavailability will help to reduce the overall size of the dose utilized and therefore reduce the amount of product exposure in our clinical intervention studies. This will increase the likelihood that a Cannabis company can supply the necessary amount of product and reduce the overall cost associated with the studies. Generally speaking, based on current literature published around CBD administration for therapeutic application, higher doses of CBD (i.e., 50mg/kg/d) were found to correlate to more positive outcomes than lower doses (i.e., 1mg/kg/d). Assuming an average weight of 70 kg, a 1000 mg dose would be around 14.29 mg/kg, and a 3000 mg dose around 42.86 mg/kg. This will allow us to investigate the pharmacokinetics of CBD on both ends of the hypothetical efficacy trend. Studies have examined single orally administered doses up to 6000 mg with no serious adverse effects reported.

Eligibility criteria: Inclusion Criteria:

1. Age 18 - 35 years old
2. Clinical labs within the stated normal range of the Royal University Hospital Test Centre, or values outside the stated normal range that are not of clinical significance as determined by the qualified investigator.
3. No clinically significant disease on medical history or clinically significant findings on physical examination including vital signs as determined by the qualified investigator.
4. Ability to stay in the clinic trial unit for 13 hours on the day of each single oral dose.
5. Ability to return for blood draws in the subsequent days.

Exclusion Criteria:

1. History or presence of significant gastrointestinal, liver or kidney disease or any other condition known to interfere with drug pharmacokinetics including bioavailability or increase risk of adverse effects.
2. History or presence of serious cardiovascular disease, such as ischaemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure
3. Males whose partners are trying to conceive (i.e. male subjects intending to start a family during the study period)
4. Lack of medically acceptable contraception by participants whose female partners have childbearing potential for the duration of the study.
5. Personal or family history of schizophrenia or any other psychotic disorder
6. Current or past drug or alcohol dependence or abuse
7. Use of Cannabis-based therapy within 2 months (Participants who have previously used a Cannabis-based therapy may be included if they have a 2-month period without use of Cannabis-based therapy prior to enrolment in the study)
8. Use of recreational Cannabis within 2 months (Participants who have previously used recreational Cannabis may be included if they have a 2-month period without use of recreational Cannabis prior to enrolment in the study)
9. Use of psychotropic medications with serotonergic activity (e.g. Selective Serotonin Reuptake Inhibitors, Tricyclic Antidepressants, Atypical Neuroleptics) within one week
10. Use of narcotic medications (e.g. Codeine, Morphine, Oxycontin) within one week
11. Use of any other medication known to interact with medicinal Cannabis within one week.
12. Allergy or known intolerance to any of the compounds within the study preparation.
13. Resting heart rate HR \< 50 bpm or \> 100 bpm or seated blood pressure \< 100/60 or higher than 140/90
14. Inability of study participants to attend and complete all study visits
15. Bleeding disorder
16. Known low hematocrit

Primary outcomes:
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Pharmacokinetic Parameters
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
Secondary outcomes:
measure: Safety of the drug using the Integrated Addendum to ICH E6(R1)
timeFrame: During the first week of administration and the 4th week of administration
measure: Safety of the drug using the Integrated Addendum to ICH E6(R1)
timeFrame: During the first week of administration and the 4th week of administration
measure: Safety of the drug using the Integrated Addendum to ICH E6(R1)
timeFrame: During the first week of administration and the 4th week of administration
measure: Optimal washout periods
timeFrame: 3 weeks
measure: Tolerability of the drug using the Integrated Addendum to ICH E6(R1)
timeFrame: During the first week of administration and the 4th week of administration
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
measure: Compare Fed vs Fast state on oral absorption kinetics
timeFrame: 1 week of samples will be collected. 2 week washout. Then another week of samples after cross over
Other outcomes:
Locations:
city: Saskatoon
country: Canada
facility: University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: Pasqua Hospital
name: Payam Dehghani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Saskatchewan
name: Jane Alcorn, DVM;PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Saskatchewan
name: Abdul Salama, PharmD
role: STUDY_DIRECTOR
References: