The Pharmacokinetics of Single Dose Oral Tetrahydrocannabinol and Cannabidiol

Chronic Kidney Diseases Clinical Trial

— POT-GFR-PK  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05742724
• Other study ID #: POT_GFR_PK_001
• Status: Recruiting
• Phase: Phase 1
• Start date: January 11, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2023
• Source: McMaster University
• Contact: Michael Walsh, MD, PhD
• Phone: 905-522-1155
• Email: lastwalsh1975[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cannabis
• Chronic Kidney Diseases
• Dialysis
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Tetrahydrocannabinol-Cannabidiol Combination
Oral THC 0.1mg/kg and CBD 2.5mg/kg

Locations

Country	Name	City	State
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	Center for Medicinal Cannabis Research

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tetrahydrocannabinol and its metabolites maximum concentration (Cmax)	Maximum concentration (Cmax)	48 hours
Primary	Tetrahydrocannabinol and its metabolites time to Cmax	Time to Cmax	48 hours
Primary	Tetrahydrocannabinol and its metabolites last detection time	Last detection time	48 hours
Primary	Tetrahydrocannabinol and its metabolites area under the curve	Area under the curve	48 hours
Primary	Tetrahydrocannabinol and its metabolites renal clearance	Renal clearance	48 hours
Primary	Tetrahydrocannabinol and its metabolites dialytic clearance	Dialytic clearance	48 hours
Primary	Cannabidiol and its metabolites maximum concentration (Cmax)	Maximum concentration (Cmax)	48 hours
Primary	Cannabidiol and its metabolites time to Cmax	Time to Cmax	48 hours
Primary	Cannabidiol and its metabolites last detection time	Last detection time	48 hours
Primary	Cannabidiol and its metabolites area under the curve	Area under the curve	48 hours
Primary	Cannabidiol and its metabolites renal clearance	Renal clearance	48 hours
Primary	Cannabidiol and its metabolites dialytic clearance	Dialytic clearance	48 hours
Primary	Other cannabinoids and their metabolites maximum concentration (Cmax)	Maximum concentration (Cmax)	48 hours
Primary	Other cannabinoids and their metabolites time to Cmax	Time to Cmax	48 hours
Primary	Other cannabinoids and their metabolites last detection time	Last detection time	48 hours
Primary	Other cannabinoids and their metabolites area under the curve	Area under the curve	48 hours
Primary	Other cannabinoids and their metabolites renal clearance	Renal clearance	48 hours
Primary	Other cannabinoids and their metabolites dialytic clearance	Dialytic clearance	48 hours
Secondary	Adverse events	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	48 hours
Secondary	Blood pressure	Systolic and diastolic blood pressure in mmHg	48 hours
Secondary	Heart rate	Heart rate in beats per minute	48 hours