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Trial registered on ANZCTR


Registration number
ACTRN12623000730606
Ethics application status
Approved
Date submitted
12/05/2023
Date registered
5/07/2023
Date last updated
12/01/2024
Date data sharing statement initially provided
5/07/2023
Date results information initially provided
12/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, 2-Part, Open-Label, Pilot Trial to Assess the Relative Bioavailability of 3 Formulations of Cannabidiol (CBD) under FASTED (Part A) and FED (Part B) conditions in Healthy Adult Male Subjects.
Scientific title
A Phase 1, 2-Part, Open-Label, Pilot Trial to Assess the Relative Bioavailability of 3 Formulations of Cannabidiol (CBD) under FASTED (Part A) and FED (Part B) conditions in Healthy Adult Male Subjects
Secondary ID [1] 309362 0
SAP021
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neurological
 329578 0
Condition category
Condition code
Neurological 326497 326497 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-center, Phase 1, randomized, open-label, 3-treatment, 4-period, 3-sequence crossover study designed to compare the relative bioavailability of two novel CBD formulations (SAP-021-T1 and SAP-021-T2) and reference formulation (Epidiolex) under fasting conditions and to evaluate the effect of food on the bioavailability SAP-021-T1 or SAP-021-T2 in healthy male subjects.

The study will be divided into two parts:
Part A: Three treatment periods, single dose, crossover study, fasting after minimum 10 hour fast with 240ml of water permitted to swallow the tablets.
Part B: One treatment period, single dose, food-effect, under fed conditions with a high calorie breakfast.

In each treatment period, subjects will be administered a study drug based on their randomization sequence under fasting or fed conditions, followed by 96 hours of PK and safety assessments.

Treatment A (Reference): 350 mg CBD (100 mg/mL CBD solution) Epidiolex administered orally under fasting conditions.
Treatment B (Test): 350 mg CBD (87.5 mg capsules) SAP-021-T1 administered orally under fasting conditions
Treatment C (Test): 350 mg CBD (87.5 mg capsules) SAP-021-T2 administered orally under fasting conditions.
Treatment D (Test): 350 mg CBD (SAP-021-T1 or SAP-021-T2 based on the PK and safety data from study Part A), administered orally after a standard high-fat diet. Participants from part A will receive treatment D (Part B) post completion of treatment A,B, and C after under fasting conditions (Part A).


Part A will consist of three treatment periods. A total of 15 subjects will be enrolled and randomized in one of three sequences, with a total of 5 subjects per sequence (n=5). Subjects will receive a single dose of one of the three CBD formulations in each period, based on the randomization schedule. There will be at least a 7-day (and no more than 14 days) washout between dosing. Participants will be monitored for dosing adherence via supervised dosing.

Following at least 2 weeks washout period following last dose administration in Part A, subjects will return to continue in study Part B. All subjects will receive a single dose of one test CBD formulation (SAP-021-T1 or SAP-021-T2 based on the decision made by SRC), thirty minutes after the start of the high-fat, high-calorie breakfast consisting of bread with butter, and bacon. The high calorie meal will follow FDA requirements of greater than 50% fat and between 800-1000Kcal. Participants will be monitored for dosing adherence via supervised dosing.
Intervention code [1] 325795 0
Treatment: Drugs
Comparator / control treatment
Epidiolex 350mg – Oral Solution (100mg/mL CBD)
Control group
Active

Outcomes
Primary outcome [1] 334346 0
To assess the relative bioavailability of two novel CBD formulations (SAP-021-T1 and SAP-021-T2) compared to the reference formulation (Epidiolex) under fasting condition in healthy adult male subjects using plasma samples
Timepoint [1] 334346 0
PK analysis for samples collected at pre-dose, 5 min, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24-, 48-, 72- and 96-hours postdose.
Primary outcome [2] 334348 0
A composite primary outcome evaluating the effect of a high-fat, high-calorie meal on the bioavailability of the active ingredient CBD and its major metabolites 7-hydroxy-cannabidiol (7- OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD), following a single dose of SAP-021-T1 or SAP-021-T2 in plasma samples of healthy adult male subjects
Timepoint [2] 334348 0
PK analysis for samples collected at pre-dose, 5 min, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24-, 48-, 72- and 96-hours postdose.
Secondary outcome [1] 420315 0
To determine the PK profiles of CBD and its major metabolites (7-OH-CBD, 7-COOH-CBD) in plasma samples following a single oral dose administration of the reference (Epidiolex) and two novel CBD formulations in healthy adult male subjects. Components to be assess are Cmax, Tmax, AUC0-t
Timepoint [1] 420315 0
PK analysis for samples collected at pre-dose, 5 min, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24-, 48-, 72- and 96-hours postdose.
Secondary outcome [2] 420316 0
To evaluate the safety and tolerability of two novel CBD formulations compared with reference formulation (Epidiolex) when administered to healthy adult male subjects.

Incidence, severity and relationship of Adverse Events (AEs) as reported by participants or documented in medical records

Incidence of Serious AEs (SAEs) and suspected unexpected SAEs as reported by participants or documented in medical records

Incidence of AEs of special interest (AESI) – abnormal clinically significant LFTs values (AST, ALT, total bilirubin)

Changes from baseline in clinical parameters (including hematology, biochemistry, coagulation, and urinalysis)

Physical examination findings as reported by participants or documented in medical records

Vital signs measurement (blood pressure [BP] and heart rate [HR] via sphygmomanometer, respiratory rate [RR] via finger pulse oximetry, and body temperature [BT] via thermometer)

12-lead electrocardiogram (ECG) recordings
Timepoint [2] 420316 0
AEs, SAEs, AESIs measured from screening until EOT Visit (D33)

Changes from baseline in clinical parameters (including hematology, biochemistry, coagulation, and urinalysis) measured on days 2, 3, 9, 10, 18, 19, 30, 31 post dose

Physical examination findings as reported by participants or documented in medical records measured from screening until EOT Visit (D33 post dose)

Vital signs measurement (blood pressure [BP], heart rate [HR], respiratory rate [RR], and body temperature [BT]) from screening until EOT Visit (D33 post dose)

12-lead electrocardiogram (ECG) recordings measured on days 1, 8, 15, 29, 33 post dose

Eligibility
Key inclusion criteria
1. Male, non-smoker (no use of tobacco or nicotine products within 1 month prior to screening), aged between 18 and 55 years (inclusive), with BMI >18.0 and <32.0 kg/m2 and body weight greater than or equal to 50.0 kg.
2. No know allergic reaction to cannabis products with previous use.
3. No known allergic reaction to sesame oil (Epidiolex is formulated in sesame oil).
4. Must have hepatic and renal clinical laboratory test results (ALT, AST, total bilirubin and eGFR) within a laboratory defined normal range.
5. Must be abstinent from heterosexual intercourse or agree to use an acceptable form of contraception with a female sexual partner of childbearing potential.
6. Refrain from donating sperm for the duration of the study and for at least 90 days after the last dose of IP.
7. Adequate venous access in both arms for collection of a number of blood samples.
8. Willing to take off dentures or mouth piercings at the time of dosing.
9. Willing and able to adhere to all protocol requirements, including willingness to comply with scheduled visits, and consume high-fat, high-calorie meal.
10. Able to understand the study procedures and provide signed informed consent form (ICF) to participate in the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any clinically significant illness or disease (in the opinion the Investigator) as determined by their medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory determinations.
2. History of inherent cardiac abnormalities based on the opinion of the Investigator.
3. Clinically significant ECG abnormalities (QTcF > 450 ms), or clinically significant vital sign abnormalities (systolic BP lower than 90 or over 140 mmHg, diastolic BP lower than 50 or over 90 mmHg, HR less than 45 or over 100 bpm, or RR less than 8 or over 22 resp/min) at screening.
4. Any laboratory test results deemed clinically significant by the Investigator or positive test serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at screening.
5. Presence of current psychiatric condition, suicide ideations or psychiatric condition requiring pharmacological management within the last 6 months, presence of current or history of psychosis/schizophrenia and bipolar disorders.
6. History of gastrointestinal disorders which may have impacted absorption, distribution, metabolism and/or excretion of the IPs (such a cholecystitis, cholecystectomy, Gilbert’s syndrome).
7. Positive urine drug screen, urine cotinine test at screening or Day -1, 7±7, 14±7 and 28±7
8. Positive alcohol breath test at screening or at admissions on Days 1, 7±7, 14±7 and 28±7.
9. Known allergic reactions to any excipient in the formulations.
10. History of significant drug abuse within 1 year prior to screening or use of drugs such as marijuana within 1 month prior to the screening visit or drugs such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening.
11. Patients with current or past history of acute or chronic liver disease of any aetiology
12. Active hepatitis – chronic or acute
13. History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit that exceeds 14 units of alcohol per week (1 unit = 150 mL of wine, 375 mL of mid strength beer, or 30 mL of distilled alcohol 40%).
14. Use of medications for the timeframes specified below, with the exception of medications exempted by the PI on a case-by-case basis because they are judged unlikely to affect the PK profile of the study drug or subject safety (e.g., topical drug products without significant systemic absorption):
a) Prescription medications within 14 days prior to the first dose until end of the study;
b) Any vaccination, within 1 month prior to the first dose through to EOS;
c) Over-the-counter products and natural health products (including herbal remedies such as St. John’s wort, homeopathic and traditional medicines), within 7 days prior to the first dose up to EOS, with the exception of the occasional use of paracetamol (up to 2 g daily) and ibuprofen (up to 1.2 g daily). Probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements are allowed;
d) Any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to the first dose.
15. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days (or a minimum of 5 half-lives, whichever is longer) prior to the first dose, administration of a biological product in the context of a clinical research study within 90 days prior to the first dose, or concomitant participation in an investigational study involving no drug or device administration.
16. Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 4 weeks prior to dosing.
17. Presence of orthodontic braces or orthodontic retention wires, or any physical findings in the mouth or tongue that would be likely to interfere with successful completion of the dosing procedure.
18. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

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)
Methods used to generate the sequence in which subjects will be randomised (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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/09/2023
Actual
26/09/2023
Date of last participant enrolment
Anticipated
5/09/2023
Actual
3/10/2023
Date of last data collection
Anticipated
27/10/2023
Actual
19/11/2023
Sample size
Target
15
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 313559 0
Commercial sector/Industry
Name [1] 313559 0
Sapient Therapeutics (Australia) PTY Ltd
Country [1] 313559 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Sapient Therapeutics (Australia) PTY Ltd
Address
Level 7 Collins Street, Melbourne, 3000, VIC, Australia
Country
Australia
Secondary sponsor category [1] 315338 0
None
Name [1] 315338 0
Address [1] 315338 0
Country [1] 315338 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312739 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 312739 0
The Alfred, 55 Commercial Road, Melbourne VIC 3004
Ethics committee country [1] 312739 0
Australia
Date submitted for ethics approval [1] 312739 0
22/05/2023
Approval date [1] 312739 0
28/06/2023
Ethics approval number [1] 312739 0

Summary
Brief summary
This is a single-center, Phase 1, randomized, open-label, 3-treatment, 4-period, 3-sequence crossover study designed to compare the relative bioavailability of two novel CBD formulations (SAP-021-T1 and SAP-021-T2) and reference formulation (Epidiolex) under fasting conditions and to evaluate the effect of food on the bioavailability SAP-021-T1 or SAP-021-T2 in healthy male subjects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125734 0
Dr Sam Francis
Address 125734 0
Nucleus Network Pty Ltd

Level 5, 89 Commercial Road

Melbourne VIC 3004
Country 125734 0
Australia
Phone 125734 0
+61 0466640801
Fax 125734 0
Email 125734 0
s.francis@nucleusnetwork.com.au
Contact person for public queries
Name 125735 0
Dr Sam Francis
Address 125735 0
Nucleus Network Pty Ltd

Level 5, 89 Commercial Road

Melbourne VIC 3004
Country 125735 0
Australia
Phone 125735 0
+61 0466640801
Fax 125735 0
Email 125735 0
s.francis@nucleusnetwork.com.au
Contact person for scientific queries
Name 125736 0
Dr Andrew Saich
Address 125736 0
Sapient Therapeutics Ltd. 120 Cockfosters Road, Barnet, United Kingdom, EN4 0DZ
Country 125736 0
United Kingdom
Phone 125736 0
+61422156206
Fax 125736 0
Email 125736 0
asaich@sapienttx.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.