CTRI/2025/04/085828 [Registered on: 28/04/2025] Trial Registered Prospectively
Last Modified On:
11/04/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Nutraceutical
Study Design
Randomized, Crossover Trial
Public Title of Study
Oral Bioequivalence Study of Cannabidiol (CBD) 600 mg Tablets in healthy volunteers under fasting study.
Scientific Title of Study
An Open Label, Single-Center, Balanced, Randomized, Multi-Dose, Two-Treatment, Two-Sequence, Two-Period, Crossover Oral Bioequivalence Study Comparing Test Product (T) Encapsulated Nano-Cannabidiol-600mg, uncoated tablets manufactured by Dhee Lifesciences with Reference Product (R) EPIDIOLEX® (cannabidiol) oral solution 100mg/mL Distributed by Jazz Pharmaceuticals, Manufactured By: GW Pharmaceuticals plc. in Healthy, Adult, Human Subjects Under Fasting Conditions.
Trial Acronym
Nil
Secondary IDs if Any
Secondary ID
Identifier
445-25 Version: 00 Dated: 10-Mar-2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Shailender Singh Tanwar MBBS
Designation
Principal Investigator
Affiliation
BioRadius Therapeutic Research Pvt. Ltd.
Address
BioRadius Therapeutic Research Pvt. Ltd.,
IndiaLand Global Industrial Park,
Plot No.8, S.No. 234, 235, 245,
Hinjawadi Phase I,
Pune, Maharashtra, India.
Pune MAHARASHTRA 411057 India
Phone
9892023392
Fax
Email
drshailendersingh.bioradiuscro@gmail.com
Details of Contact Person Scientific Query
Name
Dr Senthil Thyagrajan
Designation
Head CRO
Affiliation
BioRadius Therapeutic Research Pvt. Ltd.
Address
BioRadius Therapeutic Research Pvt. Ltd.
IndiaLand Global Industrial Park
Plot No.8, S.No. 234, 235, 245
Hinjawadi Phase I
Pune, Maharashtra, India
Pune MAHARASHTRA 411057 India
Phone
9112126448
Fax
Email
head@bioradiuscro.com
Details of Contact Person Public Query
Name
Dr Senthil Thyagrajan
Designation
Head CRO
Affiliation
BioRadius Therapeutic Research Pvt. Ltd.
Address
BioRadius Therapeutic Research Pvt. Ltd.
IndiaLand Global Industrial Park
Plot No.8, S.No. 234, 235, 245
Hinjawadi Phase I
Pune, Maharashtra, India
IndiaLand Global Industrial Park,
Plot No.8, S. No. 234, 235, 245,
Hinjawadi Phase I Pune -411057, Maharashtra, India. Pune MAHARASHTRA
9892023392
drshailendersingh.bioradiuscro@gmail.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Skinovate Independent Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Healthy adult male and female volunteers (18–45 years), with BMI 18.5–30.0 kg/m², free from significant medical conditions as confirmed by clinical evaluation and laboratory tests.
Each subject will be administered a single tablet of the test product — Encapsulated Nano- Cannabidiol 600 mg (uncoated tablets) manufactured by Dhee Lifesciences —twice daily, once in the morning and once in the evening, as per the randomization schedule in each period.
Subjects will be housed in the clinical facility of BioRadius Therapeutics Research Pvt. Ltd., Pune, for a duration sufficient to maintain their fasting condition for at least 10.00 hours prior to dosing in each period. Subjects will be checked out from the clinical facility after the collection of the 12.00 hour sample post 6th dose at Day 04. Subsequent blood sample collections on Day 04, Day 05, and Day 06 will be conducted on an ambulatory basis, as per the study protocol. This is a two-period crossover study with a minimum washout period of
13 days between Dose 6 in Period I and Dose 1 in Period II.
The total expected study duration for each subject will be at least 23 days, starting from the check-in on of Period I until the last sample collection in Period II.
The Test product (T) Encapsulated Nano-Cannabidiol-600mg, uncoated tablets manufactured by Dhee Lifesciences, allocated as per the randomization schedule, will be administered to each subject orally while in a sitting position and the subject will be instructed to swallow it with approximately 240 ± 02 mL of water at ambient temperature. Subjects who receive the Reference Product (R) will be instructed not to chew or crush the investigational product but to consume it as a whole with 240 ± 02 mL of water.
Comparator Agent
EPIDIOLEX® (cannabidiol) oral solution 100mg/mL Distributed by Jazz Pharmaceuticals, Manufactured By: GW Pharmaceuticals plc.
Each subject will be administered a single oral dose of 6 mL of the reference product EPIDIOLEX® (cannabidiol) oral solution 100 mg/mL, distributed by Jazz Pharmaceuticals, Inc. Manufactured By: GW Pharmaceuticals plc. — twice daily, once in the morning and once in the evening, as per the randomization schedule in each period.
Subjects will be housed in the clinical facility of BioRadius Therapeutics Research Pvt. Ltd., Pune, for a duration sufficient to maintain their fasting condition for at least 10.00 hours prior to dosing in each period.
Subjects will be checked out from the clinical facility after the collection of the 12.00 hour sample post 6th dose at Day 04. Subsequent blood sample collections on Day 04, Day 05, and Day 06 will be conducted on an ambulatory basis, as per the study protocol.
This is a two-period crossover study with a minimum washout period of 13 days between Dose 6 in Period I and Dose 1 in Period II. The total expected study duration for each subject will be at least 23 days, starting from the check-in on of Period I until the last sample collection in Period II.
Subjects assigned to the Reference Product (R) will receive a single dose of 6 ml (equivalent to 600 mg of Cannabidiol) of EPIDIOLEX® (cannabidiol) oral solution 100mg/mL Distributed by Jazz Pharmaceuticals, Manufactured By: GW Pharmaceuticals plc. . The study personnel will administer the dose into the subject’s mouth using a 05 mL syringe while the subject is in a sitting position. The subject will be instructed to swallow it with approximately 50 mL of water from 240 ± 02 mL of dosing water at ambient temperature. Part of the remaining water (approximately 02 x 05 mL) will be used to carefully rinse the dispensed syringe twice, and the rinsing will be directly administered into the subject’s mouth. The remaining portion of water will then be given to the
subject for drinking, ensuring complete administration of the dispensed investigational product.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
45.00 Year(s)
Gender
Both
Details
For Both Male and Female Volunteers
Healthy volunteer age 18 to 45 years weight equal to or greater than 50 kg
Willing and able to give written informed consent
BMI between 18.50 and 30.00 kg per meter squared
Healthy as per personal and medical history and general examination
No significant disease as judged by the investigator
Normal or clinically insignificant laboratory parameters within 21 days before Period I
Normal or clinically insignificant 12 lead ECG
Negative for HIV Hepatitis B and Hepatitis C and VDRL
Negative urine drug screen for THC AMP BAR COC BZO MOR or OPI
Negative breath alcohol test
Non smoker
Non alcoholic
Able to fast 10 hours before and 2 hours after morning dose
Able to fast 4 hours before and 2 hours after evening dose
Able to consume standard meals
Able to provide valid identity proof
For Female Volunteers Only
Female of childbearing potential must have a negative urine pregnancy test performed within 21 days prior to initiation of the study and must have a negative serum beta human chorionic gonadotropin beta HCG pregnancy test prior to check-in of each period
Female currently not pregnant not lactating or not attempting to become pregnant for 4 weeks before the screening visit throughout the duration of the study and 3 weeks after the subjects last study-related visit for eligible subjects only if applicable has a negative pregnancy test and is of non-childbearing potential defined as
At least 1 year post-menopausal no menstrual period for at least 12 consecutive months without any other medical cause
Surgically sterile bilateral tubal ligation bilateral oophorectomy or hysterectomy
Or
Of childbearing potential and willing to commit to using a consistent and acceptable method of birth control as defined below for the duration of the study
Double barrier methods such as condoms cervical cap diaphragm and vaginal contraceptive film with spermicide
Intrauterine device IUD with a low failure rate less than 1 percent per year
Or
Of childbearing potential and not sexually active willing to commit to using a consistent and acceptable method of birth control as defined above for the duration of the study in the event the subject becomes sexually active.
ExclusionCriteria
Details
For Both Male and Female Volunteers:
1.Any significant medical disorder (as per investigator’s opinion).
2.Major surgery in the past 3 months.
3.History of dialysis.
4.Significant history/presence of disorders (haemopoetic, cardiac, liver, kidney, GI, endocrine, neuro, psych, etc.).
5.History/presence of diabetes, TB, or systemic hypertension.
6.Medications for joint pain, inflammation, kidney/urinary stones.
7.Dehydration due to vomiting/diarrhoea within 24 hrs before check-in.
8.History of dysphasia.
9.History or presence of cancer.
10.Difficulty in blood donation.
11.Personal/family history of muscular disorders.
12.Deformity affecting venous access.
13.Significant medical disorder (duplicate of point 1).
14.Unable to abstain from caffeine/xanthine-containing products.
15.Intake of caffeine/xanthine products within 24 hrs of check-in.
16.Use of tobacco or grapefruit (and juice) within 48 hrs of check-in.
17.Positive breath alcohol or urine drug screen at check-in.
18.History of drug abuse.
19.History of alcohol consumption.
20.Food/vegetable allergies or hypersensitivity reactions.
21.Use of medications that could affect study drug kinetics/dynamics.
22.Participation in drug research or blood donation within last 90 days.
23.Positive for HIV, Hepatitis B/C, or VDRL.
24.Use of OTC/herbal meds within 7 days before check-in.
25.Use of prescription meds affecting study drug within 14 days.
26.Unusual diet (e.g., low sodium) within 3 weeks before check-in.
27.Drug depot injection/implant in past 3 months.
28.Practicing a vegan diet.
29.Known hypersensitivity to cannabidiol or any EPIDIOLEX excipients.
For Female Volunteers Only:
30. Pregnant, lactating, planning pregnancy/gamete donation, or unwilling to use contraception during study and 3 weeks after.
31. Positive urine/serum pregnancy test during screening or before each period.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pharmacy-controlled Randomization
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
The pharmacokinetic parameters Cmax, Tmax, AUC of both products, specifically focusing on the area under the concentration-time curve AUC from time zero to the last measurable concentration AUC0-t and the area under the curve extrapolated to infinity AUC0-inf including the measurement of the 7OH metabolite levels
In each period 19 1 x 05 mL blood samples will be collected from each subject in K2EDTA vacutainers. The blood samples will be collected as per following schedule.
Pre-dose sample will be collected at
At Day 01 within 5 minutes before Dose 1 and Dose 2
At Day 02 within 5 minutes before Dose 3 and Dose 4
At Day 03 within 5 minutes before Dose 5 and Dose 6
Post-dose samples will be collected after administration of Dose 6 at
At Day 03 00.25, 00.50, 01.00, 01.50, 02.00, 03.00, 04.00 hours post dose 6
At Day 04 06.00, 08.00, 12.00, 24.00 hours post dose 6
At Day 05 48.00 hours post dose 6
At Day 06 72.00 hours post dose 6
Secondary Outcome
Outcome
TimePoints
Safety and tolerability assessments, including:
Incidence and severity of adverse events (AEs)
Changes in vital signs (blood pressure, heart rate, temperature)
Laboratory test results (hematology, biochemistry)
Subjective assessments of tolerability (using a visual analog scale for discomfort or side effects)
Vital signs (including blood pressure, pulse rate, and body temperature) will be recorded at specific intervals throughout the study. For Dose 01 to Dose 05, vital signs will be measured at 01.00 and 03.00 hours post-dose. Following administration of Dose 06, vital signs will be recorded on Day 03 and Day 04 at 01.00, 03.00, and 06.00 hours post-dose, within a ±40-minute window from the scheduled time in each period. Additionally, vital signs will also be assessed during each ambulatory sample collection, specifically on Day 04 (24.00 hours post-dose 6), Day 05 (48.00 hours post-dose 6), and Day 06 (72.00 hours post-dose 6).
Target Sample Size
Total Sample Size="24" Sample Size from India="24" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
09/05/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="0" Days="23"
Recruitment Status of Trial (Global)
Not Yet Recruiting
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase I, open-label, randomized, single-dose, two-treatment, two-period, two-sequence crossover study designed to compare the rate and extent of absorption of Encapsulated Nano-Cannabidiol Test with that of Epidiolex oral solution Reference in healthy adult volunteers under fasting conditions.
Eligible subjects will be randomized to one of two treatment sequences TR or RT and will receive a single dose of either the Test or Reference product in each study period. Each dosing period will be separated by a washout interval of at least 7 calendar days, which is considered sufficient based on the known pharmacokinetics of cannabidiol to ensure complete elimination of the drug from the body prior to the next administration.
The study will be conducted under controlled conditions in a clinical research facility. Standardized meals and fluid intake will be provided according to the protocol schedule. Subjects will be confined at the facility from at least 10 hours prior to dosing until after the 24-hour post-dose blood sample collection in each period. Blood samples for pharmacokinetic analysis will be collected at pre-defined time points up to 72 hours post-dose in each period.
Plasma concentrations of cannabidiol will be determined using a validated bioanalytical method, and pharmacokinetic parameters including Cmax, Tmax, AUC0–t, AUC0–inf, t1/2, and Kel will be calculated using non-compartmental analysis. The primary endpoints for bioequivalence evaluation will be Cmax, AUC0–t, and AUC0–inf. The Test product will be considered bioequivalent to the Reference product if the 90% confidence intervals for the geometric mean ratios Test/Reference for these parameters fall within the regulatory bioequivalence limits of 80.00% to 125.00%.
Safety will be monitored throughout the study through the assessment of adverse events AEs, clinical laboratory evaluations, vital signs, physical examinations, and 12-lead ECGs. All study procedures will be conducted in accordance with the principles of Good Clinical Practice GCP, the Declaration of Helsinki, and applicable regulatory guidelines.