Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000944639
Ethics application status
Approved
Date submitted
16/08/2023
Date registered
1/09/2023
Date last updated
1/11/2023
Date data sharing statement initially provided
1/09/2023
Date results information initially provided
1/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A comparison of cannabis medicines containing Cannabidiol (CBD) in healthy males
Scientific title
An open label, randomised, single oral dose, three-period, cross-over trial to assess the pharmacokinetics of Cannabidiol Oil (100 mg/mL) (reference) in comparison with two Cannabidiol 100 mg capsules (Test Drug, Swiss Manufactured and Australian Manufactured) in fasted healthy males
Secondary ID [1] 310399 0
Protocol number: CBD Compare
Universal Trial Number (UTN)
U1111-1296-6211
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic pain 331151 0
Condition category
Condition code
Alternative and Complementary Medicine 327928 327928 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is to evaluate the pharmacokinetic profiles and the relative bioavailability of CBD between the reference product (oral oil 100 mg single dose, once only) in comparison with the test products (oral Swiss manufactured capsules CBD 100 mg single dose, once only, and oral Australian manufactured capsules CBD 100 mg single dose, once only) after fasting overnight for at least 10 hours (nil by mouth), in healthy males administered at the research site. There will be a minimum of 13 days washout period between doses.
Intervention code [1] 326800 0
Treatment: Drugs
Comparator / control treatment
Cannabidiol (100 mg/mL) Oil., 100 mg orally once only administered at the research site
Control group
Active

Outcomes
Primary outcome [1] 335784 0
The primary objective is to determine the Plasma pharmacokinetics of test and reference products using Primary Variables AUC 0-tlast and Cmax, with Secondary Variables being AUC0-8, tmax and t ½.
Timepoint [1] 335784 0
Pharmacokinetic Sampling at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Secondary outcome [1] 425622 0
The secondary objective is to determine if the Swiss and Australian manufactured Satipharm capsules are bioequivalent. Plasma concentrations of cannabidiol will be analysed by Liquid Chromatography Tandem Mass Spectrometry to determine if the Swiss and Australian manufactured Satipharm capsules are bioequivalent.
Timepoint [1] 425622 0
Plasma Pharmacokinetic Sampling at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose

Eligibility
Key inclusion criteria
1. Healthy male participants aged between 18 and 40 years,
2. Ability to communicate adequately with the investigator or their representatives
3. Ability to understand and agreement to comply with the study requirements and assessments
4. Provision of written informed consent
5. Non-smokers, non-vaper
6. Negative alcohol breath test results
7. Body Mass Index ranged between 18.5-30 kg/m2
8. Normal blood pressure and heart rate measured under stabilised conditions at the screening visit after at least 5 minutes of rest under supine position: SBP within 100 to 140 mmHg, DBP within 60 to 90 mmHg and HR within 40 to 100 bpm
9. Laboratory results within normal range or clinically non-significant (FBC, glucose, urea, uric acid, creatinine, estimated GFR (eGFR), total bilirubin, sodium, potassium, calcium, chloride, SGOT (AST), SGPT (ALT), GGT, alkaline phosphatase, total protein and urinalysis), drug addiction scanning in urine results is negative (amphetamine, benzodiazepine, cannabinoid, cocaine, opiate),
10. He and his female partner will use contraception during the study and at least 7 days after the study.
11. Willing to fast overnight from 9pm, three times, prior to each treatment
Minimum age
18 Years
Maximum age
40 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Who are not suitable to any of inclusion criteria.
2. Participants suspected to have a high probability of non-compliance to the study procedure and/or completion of the study according to the investigator’s judgement,
3. Who have known allergy for cannabidiol and/or any other ingredients of the products
(excipients),
4. History of difficulty of swallowing.
5. Participants who have any chronic disease which might interfere with absorption, distribution, metabolism or excretion of the drug.
6. Any history or presence of clinical relevance of cardiovascular, neurological, musculoskeletal, haematological, hepatic, gastrointestinal (and/or GI Surgery), renal, pulmonary, endocrinological, metabolism or psychiatric disease, any type of porphyria.
7. Use of any drug including over-the-counter (OTC) that may have an interaction with Cannabidiol within 2 weeks prior to each treatment
8. History of drug or alcohol abuse, defined as diagnosed substance abuse disorder.
9. Use of any Cannabis or other illicit drug in past month, confirmed by negative drug screen
10. Regular use of more than 2 units of alcohol per day or 10 units per week and/or positive
alcohol breath test results (Note: one unit of alcohol equals 250 mL beer, 125 mL wine or 25
mL spirits).
11. Participants who have taken any grapefruit or grapefruit juice during 7 days prior to drug
administration, during the study.
12. Participants who have given more than 400 mL blood within the last two months before the first treatment and participants who have participated in any drug research within the last two months before the first treatment.
13. Participants who have a relationship with the study team.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the holder of the allocation schedule who is off-site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Sample size
The sample size is based on published EMA and FDA guidelines for bioequivalence studies.
Safety parameters
• Adverse events (AEs) will be coded and presented using CTCAE v5.0. The overall incidence, the incidence of related as well as the incidence of serious adverse events (SAEs) will be summarized per dose and by body system in tables.
• Local tolerability will be presented by overall incidence by treatment group per symptom.
• Vital signs (supine blood pressure, heart rate, body temperature and respiratory rate): Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum) will be provided for blood pressure, heart rate, body temperature and respiratory rate and for changes from baseline.
• Hematology, biochemistry and urinalysis parameters:
Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum) will be provided on values at baseline and all post-dose assessments. Descriptive statistics will be calculated on the change from baseline values. Out-of-normal-range values will be indicated for each parameter. The change in out-of-normal-range values after administration and at follow up versus baseline will be summarized per group by means of shift-tables.
Pharmacokinetic parameters:
Plasma concentrations of cannabidiol will be analysed by Liquid Chromatography Tandem Mass Spectrometry (LCMSMS)
Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum, plus Geometric mean and CV for Cmax and AUC are the derived parameters) will be provided for the PK parameters.
Statistical analysis will be performed using PKAnalix. Analysis of Variance (ANOVA), two one-sided tests and 90% confidence intervals for the geometric mean ratios (test/reference) of Cmax and AUC0-tlast will be calculated.
An acceptance range of 80% - 125% for Cmax and AUC0-tlast of CBD will be applied.
Primary Variable:
AUC 0-tlast
Cmax
Secondary Variable
AUC0-8,
tmax,
t ½

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
4/09/2023
Actual
4/09/2023
Date of last participant enrolment
Anticipated
4/10/2023
Actual
4/10/2023
Date of last data collection
Anticipated
15/11/2023
Actual
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25396 0
Novatrials - Kotara
Recruitment postcode(s) [1] 41135 0
2289 - Kotara

Funding & Sponsors
Funding source category [1] 314605 0
University
Name [1] 314605 0
The University of Newcastle, Australia
Country [1] 314605 0
Australia
Funding source category [2] 314610 0
Government body
Name [2] 314610 0
National Health and Medical Research Council
Country [2] 314610 0
Australia
Primary sponsor type
University
Name
The University of Newcastle, Australia
Address
Research and Innovation
University Drive
Callaghan, NSW 2308
Country
Australia
Secondary sponsor category [1] 316574 0
None
Name [1] 316574 0
Address [1] 316574 0
Country [1] 316574 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313634 0
Bellberry Limited
Ethics committee address [1] 313634 0
123 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 313634 0
Australia
Date submitted for ethics approval [1] 313634 0
29/03/2023
Approval date [1] 313634 0
18/08/2023
Ethics approval number [1] 313634 0
2023-03-350

Summary
Brief summary
The proposed clinical trial will evaluate the bioavailability of Satipharm CBD capsules compared to a CBD oil at a dose of 100mg. The trial will also determine if there is bioequivalence between the Swiss manufactured Satipharm CBD capsules and Australian manufactured CBD capsules.
12 healthy male participants will receive one single oral dose of 100 mg cannabidiol (1mL of the reference drug or two tablets of the test drug) after an overnight fast in each of the 3 periods according to a sequence determined by randomisation.
In each study period, participants will take different products (either one dose of the 2 Test Drugs or one dose of Reference Drug) with a minimum 13 day wash-out between each study period. The study hypothesis is that the Australian manufactured CBD capsules will show an equivalent bioavailability at the specified time points to that of the Swiss manufactured CBC capsules.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128814 0
Prof Jennifer Martin
Address 128814 0
Chair of Clinical Pharmacology, School of Medicine and Public Health, and Director of ACREUniversity of NewcastleUniversity DriveCallaghan NSW 2308
Country 128814 0
Australia
Phone 128814 0
+61 2 4042 0908
Fax 128814 0
Email 128814 0
jenniferh.martin@newcastle.edu.au
Contact person for public queries
Name 128815 0
Ms Sarah Fitzpatrick
Address 128815 0
NovatrialsLevel 1 OTP House10 Bradford CloseKotara NSW 2289
Country 128815 0
Australia
Phone 128815 0
+61 2 4058 5491
Fax 128815 0
+61 2 4089 3747
Email 128815 0
sfitzpatrick@novatrials.com.au
Contact person for scientific queries
Name 128816 0
Prof Jennifer Martin
Address 128816 0
Chair of Clinical Pharmacology, School of Medicine and Public Health, and Director of ACREUniversity of NewcastleUniversity DriveCallaghan NSW 2308
Country 128816 0
Australia
Phone 128816 0
+61 2 4042 0908
Fax 128816 0
Email 128816 0
jenniferh.martin@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The final cleaned non-identified data set will be available for dissemination in line with NHMRC revised
Statement for Ethical Conduct in Human Research 2007, (updated 2018).
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Anyone who wishes to access the data
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Access subject to approval by Principal Investigator, email: jenniferh.martin@newcastle.edu.au


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.