POT-GFR-PK: The Pharmacokinetics of Single Dose Oral Tetrahydrocannabinol and Cannabidiol

Sponsor

McMaster University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05742724

Collaborator

Center for Medicinal Cannabis Research (Other)

Enrollment

Location

Arm

11.6

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cannabis Chronic Kidney Diseases Dialysis	Drug: Tetrahydrocannabinol-Cannabidiol Combination	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

The Pharmacokinetics of Oral Tetrahydrocannabinol and Cannabidiol Across the Spectrum of Glomerular Filtration Rate: a PharmacoKinetic Study

Actual Study Start Date :

Jan 11, 2023

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: THC/CBD Oral THC 0.1mg/kg and CBD 2.5mg/kg	Drug: Tetrahydrocannabinol-Cannabidiol Combination Oral THC 0.1mg/kg and CBD 2.5mg/kg

Arm

Intervention/Treatment

Experimental: THC/CBD

Oral THC 0.1mg/kg and CBD 2.5mg/kg

Drug: Tetrahydrocannabinol-Cannabidiol Combination

Oral THC 0.1mg/kg and CBD 2.5mg/kg

Outcome Measures

Primary Outcome Measures

Tetrahydrocannabinol and its metabolites maximum concentration (Cmax) [48 hours]
Maximum concentration (Cmax)
Tetrahydrocannabinol and its metabolites time to Cmax [48 hours]
Time to Cmax
Tetrahydrocannabinol and its metabolites last detection time [48 hours]
Last detection time
Tetrahydrocannabinol and its metabolites area under the curve [48 hours]
Area under the curve
Tetrahydrocannabinol and its metabolites renal clearance [48 hours]
Renal clearance
Tetrahydrocannabinol and its metabolites dialytic clearance [48 hours]
Dialytic clearance
Cannabidiol and its metabolites maximum concentration (Cmax) [48 hours]
Maximum concentration (Cmax)
Cannabidiol and its metabolites time to Cmax [48 hours]
Time to Cmax
Cannabidiol and its metabolites last detection time [48 hours]
Last detection time
Cannabidiol and its metabolites area under the curve [48 hours]
Area under the curve
Cannabidiol and its metabolites renal clearance [48 hours]
Renal clearance
Cannabidiol and its metabolites dialytic clearance [48 hours]
Dialytic clearance
Other cannabinoids and their metabolites maximum concentration (Cmax) [48 hours]
Maximum concentration (Cmax)
Other cannabinoids and their metabolites time to Cmax [48 hours]
Time to Cmax
Other cannabinoids and their metabolites last detection time [48 hours]
Last detection time
Other cannabinoids and their metabolites area under the curve [48 hours]
Area under the curve
Other cannabinoids and their metabolites renal clearance [48 hours]
Renal clearance
Other cannabinoids and their metabolites dialytic clearance [48 hours]
Dialytic clearance

Secondary Outcome Measures

Adverse events [48 hours]
Weakness, fatigue, pain, falls, abnormal coordination, numbness or tingling, sedation, sleepiness, tremor, confusion, disorientation, dissociation, abnormal speech, muscle spasms, nausea, vomiting, diarrhea, altered mood, depression, euphoric mood, hallucinations, blurred vision, dizziness, imbalance, palpitations, hypotension, syncope, urinary tract infection, allergic reactions, shortness of breath, lung infection, fever, sweatiness, headache
Blood pressure [48 hours]
Systolic and diastolic blood pressure in mmHg
Heart rate [48 hours]
Heart rate in beats per minute

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

adult age>25 years
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
agree to take the medication as directed in the study
provides informed consent

Exclusion Criteria:

body mass index <20 or >35kg/m2
physical dependence on any drug other than caffeine or nicotine
history of clinically significant adverse event associated with cannabis intoxication
history of psychosis or mania or any active major psychiatric disorder
recent (within 30 days) use of any cannabinoid (natural or synthetic) identified by self-report or urine drug screen for cannabinoids
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)
evidence of liver dysfunction (ALT less than 3 times upper limit of normal, bilirubin below upper limit of normal, international normalized ratio<1.5)
pregnant or breastfeeding women
change in ideal body weight or dry weight in the last 4 weeks
intradialytic hypotension (systolic blood pressure<90mmHg) requiring an intervention in the previous 4 weeks