Clinical trial NCT05742724: The Pharmacokinetics of Single Dose Oral Tetrahydrocannabinol and Cannabidiol
Official title: The Pharmacokinetics of Oral Tetrahydrocannabinol and Cannabidiol Across the Spectrum of Glomerular Filtration Rate: a PharmacoKinetic Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Cannabis
Chronic Kidney Diseases
Dialysis
Keywords: Pharmacokinetics
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Center for Medicinal Cannabis Research
First posted: 2023-02-24
Enrollment: 24
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: POT-GFR-PK is a single dose pharmacokinetic study oral tetrahydrocannabinol (THC) and cannabidiol (CBD) in healthy adult controls and individuals with chronic kidney disease including those treated with in-center hemodialysis.

Detailed description: Adults aged greater than 25 years including 6 with eGFR\>60ml/min/1.73m2, 6 eGFR 30-59ml/min/1.73m2, 6 eGFR \<30ml/min/1.73m2 (CKD Epidemiology Collaboration equation) and 6 receiving in-center hemodialysis at least 2x weekly via a tunnelled catheter will receive THC 0.1mg/kg and CBD 2mg/kg by mouth in the form of MediPharm Labs-001 (MPL-001) (50mg CBD/2mg THC per 1mL). In healthy controls and participants with chronic kidney disease, blood samples will be collected at t=0, 1, 2, 3, 3.5 and 4 hours post THC/CBD administration. In participants receiving in-center hemodialysis, blood samples will be collected at t=0, 1, 2, 3, 3.5 and 4 hours post THC/CBD administration and during hemodialysis at t=0, 60, 120, 180 minutes and 15 minutes prior to the end of hemodialysis (at a reduced pump speed with blood flow 50-100ml/min) and 60 minutes post-hemodialysis. A 24 hour urine will be collected in all participants except those receiving hemodialysis without any residual urine output. Dialysate samples will be collected at 1,2,3 hours during hemodialysis and at the end of hemodialysis. Blood samples will also be collected at 24 and 48 hours. Plasma, urine and dialysis cannabinoids (THC, CBD and their metabolites) will be quantified using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry.

Eligibility criteria: Inclusion Criteria:

1. adult age\>25 years
2. estimated glomerular filtration rate (eGFR)\>60ml/min/1.73m2 or eGFR\<60ml/min/1.73m2 by the CKD Epidemiology Collaboration equation including in-center hemodialysis at least 2x weekly for a minimum of 3 hours per treatment via a tunnelled catheter treated \>90 days
3. agree to take the medication as directed in the study
4. provides informed consent

Exclusion Criteria:

1. body mass index \<20 or \>35kg/m2
2. physical dependence on any drug other than caffeine or nicotine
3. history of clinically significant adverse event associated with cannabis intoxication
4. history of psychosis or mania or any active major psychiatric disorder
5. recent (within 30 days) use of any cannabinoid (natural or synthetic) identified by self-report or urine drug screen for cannabinoids
6. taking any medication with known interactions with THC or CBD via cytochrome P450 (CYP) CYP2C9, CYP2C19 and CYP4A6 or CYP2D4 (e.g. anti-epileptic drugs, calcineurin inhibitors, anti-fungal)
7. evidence of liver dysfunction (ALT less than 3 times upper limit of normal, bilirubin below upper limit of normal, international normalized ratio\<1.5)
8. pregnant or breastfeeding women
9. change in ideal body weight or dry weight in the last 4 weeks
10. intradialytic hypotension (systolic blood pressure\<90mmHg) requiring an intervention in the previous 4 weeks

Primary outcomes:
measure: Tetrahydrocannabinol and its metabolites maximum concentration (Cmax)
timeFrame: 48 hours
measure: Tetrahydrocannabinol and its metabolites time to Cmax
timeFrame: 48 hours
measure: Tetrahydrocannabinol and its metabolites last detection time
timeFrame: 48 hours
measure: Tetrahydrocannabinol and its metabolites area under the curve
timeFrame: 48 hours
measure: Tetrahydrocannabinol and its metabolites renal clearance
timeFrame: 48 hours
measure: Tetrahydrocannabinol and its metabolites dialytic clearance
timeFrame: 48 hours
measure: Cannabidiol and its metabolites maximum concentration (Cmax)
timeFrame: 48 hours
measure: Cannabidiol and its metabolites time to Cmax
timeFrame: 48 hours
measure: Cannabidiol and its metabolites last detection time
timeFrame: 48 hours
measure: Cannabidiol and its metabolites area under the curve
timeFrame: 48 hours
measure: Cannabidiol and its metabolites renal clearance
timeFrame: 48 hours
measure: Cannabidiol and its metabolites dialytic clearance
timeFrame: 48 hours
measure: Other cannabinoids and their metabolites maximum concentration (Cmax)
timeFrame: 48 hours
measure: Other cannabinoids and their metabolites time to Cmax
timeFrame: 48 hours
measure: Other cannabinoids and their metabolites last detection time
timeFrame: 48 hours
measure: Other cannabinoids and their metabolites area under the curve
timeFrame: 48 hours
measure: Other cannabinoids and their metabolites renal clearance
timeFrame: 48 hours
measure: Other cannabinoids and their metabolites dialytic clearance
timeFrame: 48 hours
Secondary outcomes:
measure: Adverse events
timeFrame: 48 hours
measure: Blood pressure
timeFrame: 48 hours
measure: Heart rate
timeFrame: 48 hours
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
Study officials:
affiliation: McMaster University
name: Michael Walsh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: