An Open Label, Single-Center, Multi-Dose, Single-Treatment, Single-Sequence, Single -Period, Oral Bioavailability Study of Test Product (T) Nano-Encapsulated Delayed-Release Cannabidiol Tablets 300 mg (Dose: 02 x 300mg = 600mg) manufactured by Dhee Lifesciences Pvt. Ltd., in Healthy, Adult, Human Subjects Under Fasting and Fed Conditions.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- To characterize the pharmacokinetic profile of nano-encapsulated delayed-release cannabidiol tablets Cannabidiol Tablets 300 mg (Dose: 02 x 300mg = 600mg) by determining
研究概览
简要总结
This is a Open Label, Single-Center, Multi-Dose, Single-Treatment, Single-Sequence, Single -Period, Oral Bioavailability Study of Nano-Encapsulated Delayed-Release Cannabidiol Tablets 300 mg (Dose: 02 x 300mg = 600mg in Healthy adult human volunteers under fasting and fed conditions.
Eligible subjects will receive two tablets of the Test Product (Nano-Encapsulated Delayed-Release Cannabidiol Tablets 300 mg, total 600 mg per dose) twice daily for three consecutive days and a single morning dose on Day 4, administered orally with 240 milliliters of water by trained study personnel.
Fasting Condition:Subjects will be housed at the clinical facility in Pune to maintain an overnight fast of at least 10 hours before Dose 01.
Day 01 Morning (Dose 01): Dose given after fasting.
Days 02, 03, and 04 Morning (Doses 3, 5, 7): Dose given after minimum 2-hour fasting.
Evening Doses on Days 01, 02, and 03 (Doses 2, 4, 6): Administered 12 hours after morning dose.
Fed Condition:Subjects will fast overnight for 10 hours before receiving a high-fat, high-calorie non-veg meal (950–1000 kcal).
Day 01 Morning (Dose 01): Meal given 30 minutes prior to dosing.
Days 02, 03, and 04 Morning (Doses 3, 5, 7): Same meal served 30 minutes before dose, after 2-hour fast.
Evening Doses on Days 01, 02, and 03 (Doses 2, 4, 6): Same meal protocol, followed by dosing 12 hours after morning dose.
Dosing Instructions:All doses are administered orally in sitting position, with 240 milliliters of water at ambient temperature. Tablets must be swallowed whole and not crushed or chewed.
Pharmacokinetic (PK) Analysis:Primary PK Parameters:
AUC0-t
Ct ss
Cmax ss
Secondary PK Parameters:
Tmax ss
Half-life
Elimination rate constant
Cmin ss
Cavg ss
Fluctuation percent and Swing percent
PK analysis will be performed using Phoenix WinNonlin version 8.3.3 or higher or SAS version 9.4 or higher.
Statistical Analysis:
Log-transformed values of AUC, Cmax ss, and Ct ss will be analyzed using ANOVA.
Intra-subject variability, power, geometric mean ratios, and 90 percent confidence intervals will be calculated to assess the bioavailability of the test product under fasting conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- All
入选标准
- •Healthy human volunteer of 18 to 45 years of age (both inclusive) and weight of at least 50 kg.
- •3Body Mass Index (BMI) between 18.50–30.00 Kg/m
- •4Healthy individuals as evaluated by personal history, medical history and general medical examination.
- •Absence of significant disease judged by investigator.
- •Volunteer with normal biochemical, haematological and urinary parameters or with abnormality considered to be clinically not significant and performed within 21 days prior to check in of Period I.
- •Negative HIV 1 & 2 antibodies, Hepatitis B surface antigen, Hepatitis C antibody and VDRL
- •Negative urine scan for drugs of abuse like Cannabinoids-CANNAB/Tetrahydrocannabinol-THC, Amphetamine-AMP, Barbiturates-BAR, Cocaine-COC, Benzodiazepines-BZO and Morphine-MOR/Opioid-OPI.
- •Negative breath alcohol test.
- •Non-alcoholic.
- •Ability to fast for at least 10.00 hours before the Dose 01 (Morning dose) and will continue fasting for at least 02.00 hours post-dose.
- •Ability to fast for at least 10.00 hours before the high-fat high-calorie breakfast prior to Dose 01 (Morning dose) and will continue fasting for at least 02.00 hours post-dose.
- •Ability to fast for at least 02.00 hours before the Dose 02 (Evening dose), Dose 03 (Morning dose), Dose 04 (Evening dose), Dose 05 (Morning dose), Dose 06 (Evening dose) and Dose 07 (Morning dose) and will continue fasting for at least 02.00 hours post-dose.
- •Ability to consume standard meals and high-fat, high-calorie (approximately 950 to 1000 kcal), non-veg meal.
- •Volunteer who can provide adequate evidence of their identity.
- •or 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.
排除标准
- •History of any medical disorder that is of significance in the investigator’s opinion.
- •History of any major surgical procedure in the past 3 months.
- •Present or past history of being on dialysis.
- •History or presence of significant haemopoetic, cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, urinary retention, severe gastro-intestinal condition (including toxic mega colon), myasthenia gravis, narrow-angle glaucoma, and tachyarrhythmia or psychiatric disease or disorder.
- •History or presence of diabetes mellitus, tuberculosis and systemic hypertension.
- •History or presence of any medication for treatment of joint pain, inflammation, stone in kidney or urinary tract.
- •Recent history of dehydration from diarrhoea, vomiting or any other reason within a period of 24 hours prior to check in.
- •History of dysphasia.
- •History or presence of cancer.
- •Difficulty in donating blood.
- •Personal or family history of muscular disorders
- •Volunteer having any deformity that will affect venous access for cannulation.
- •Consumption of caffeine and /or xanthine products (i.e., coffee, tea, chocolate, and caffeine-containing sodas, colas, etc.) for at least 48.00 hours prior to check-in.
- •Consumption of tobacco containing products and grapefruit and its juice for at least 48.00 hours prior to check in.
- •Positive in breath test for alcohol consumption and urine scan for drug abuse during check-in.
- •History of any drug abuse.
- •History or presence of consumption of alcohol.
- •History of allergy to vegetables and / or food substances and / or any other manifestations suggestive of hypersensitivity reactions.
- •Present or past history of intake of medications which potentially modify kinetics / dynamics of study medications or any other medication judged to be clinically significant by the investigator.
- •Participation in a drug research study within 90 days prior to check-in or donation of blood within 90 days prior to check-in.
- •Positive screening test result for any one or more of the following: HIV, Hepatitis B, Hepatitis C and VDRL.
- •within 7 days prior to check-in.
- •Intake of any prescription medications within 14 days prior to check-in that could affect the kinetics or dynamics of study medications in view of investigator.
- •An unusual diet for whatever reason (e.g. low sodium diet) for three weeks prior to check-in.
- •Had a depot injection or an implant of any drug 3 months prior to the commencement of this study.
- •Practicing Vegan Diet.
- •History of hypersensitivity to study medications cannabidiol or any excipient in Cannabidiol (Active Ingredient: cannabidiol Inactive Ingredients: dehydrated alcohol (7.9% w/v), sesame seed oil, strawberry flavor, and sucralose.
- •Cannabidiol contains no ingredient made from a gluten-containing grain (wheat, barley, or rye)).
- •For Female Volunteers
- •Female who is pregnant or lactating, or plans to become pregnant, or donate gametes during the study period or for 3 weeks after the subject’s last study-related visit (for eligible subjects only, if applicable) and unwilling to employ appropriate contraceptive measures to ensure that pregnancy will not occur during the study.
- •Female, demonstrating positive urine pregnancy test at the time of screening and serum pregnancy test before check-in and through the duration of the study.
结局指标
主要结局
To characterize the pharmacokinetic profile of nano-encapsulated delayed-release cannabidiol tablets Cannabidiol Tablets 300 mg (Dose: 02 x 300mg = 600mg) by determining
时间窗: 31 (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 Pre-morning Dose (within 05 minutes) | At Day 02 (within 05 minutes before Dose 03 and Dose 04) | At Day 03 (within 05 minutes before Dose 05 and Dose 06) | At Day 04 (within 05 minutes before Dose 07) | At Day 01: | Post-morning dose (Dose 01): 00.50, 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, and 12.00 hours (12.00 hours Post dose 01 Samples shall be collected within 5 minutes before Dose 02) | Post-evening dose (Dose 02): 01.00, 02.00, 03.00, 04.00, 05.00 hours | At Day 04: | Post-morning dose (Dose 07): 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, 12.00, 24.00, 48.00, and 72.00 hours. | Samples from Day 01 to Day 04 up to the 12.00-hour post-dose time point will be collected in-house at the study facility. | amples collected after the Post dose 07 at 24.00, 48.00 and 72.00 hours, will be collected on an ambulatory basis. All the ambulatory samples will be collected within 04.00 hour of the scheduled sampling time point
• Area under the concentration–time curve from time zero to the last measurable concentration
时间窗: 31 (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 Pre-morning Dose (within 05 minutes) | At Day 02 (within 05 minutes before Dose 03 and Dose 04) | At Day 03 (within 05 minutes before Dose 05 and Dose 06) | At Day 04 (within 05 minutes before Dose 07) | At Day 01: | Post-morning dose (Dose 01): 00.50, 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, and 12.00 hours (12.00 hours Post dose 01 Samples shall be collected within 5 minutes before Dose 02) | Post-evening dose (Dose 02): 01.00, 02.00, 03.00, 04.00, 05.00 hours | At Day 04: | Post-morning dose (Dose 07): 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, 12.00, 24.00, 48.00, and 72.00 hours. | Samples from Day 01 to Day 04 up to the 12.00-hour post-dose time point will be collected in-house at the study facility. | amples collected after the Post dose 07 at 24.00, 48.00 and 72.00 hours, will be collected on an ambulatory basis. All the ambulatory samples will be collected within 04.00 hour of the scheduled sampling time point
• Steady-state trough concentration
时间窗: 31 (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 Pre-morning Dose (within 05 minutes) | At Day 02 (within 05 minutes before Dose 03 and Dose 04) | At Day 03 (within 05 minutes before Dose 05 and Dose 06) | At Day 04 (within 05 minutes before Dose 07) | At Day 01: | Post-morning dose (Dose 01): 00.50, 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, and 12.00 hours (12.00 hours Post dose 01 Samples shall be collected within 5 minutes before Dose 02) | Post-evening dose (Dose 02): 01.00, 02.00, 03.00, 04.00, 05.00 hours | At Day 04: | Post-morning dose (Dose 07): 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, 12.00, 24.00, 48.00, and 72.00 hours. | Samples from Day 01 to Day 04 up to the 12.00-hour post-dose time point will be collected in-house at the study facility. | amples collected after the Post dose 07 at 24.00, 48.00 and 72.00 hours, will be collected on an ambulatory basis. All the ambulatory samples will be collected within 04.00 hour of the scheduled sampling time point
• Steady-state maximum plasma concentration
时间窗: 31 (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 Pre-morning Dose (within 05 minutes) | At Day 02 (within 05 minutes before Dose 03 and Dose 04) | At Day 03 (within 05 minutes before Dose 05 and Dose 06) | At Day 04 (within 05 minutes before Dose 07) | At Day 01: | Post-morning dose (Dose 01): 00.50, 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, and 12.00 hours (12.00 hours Post dose 01 Samples shall be collected within 5 minutes before Dose 02) | Post-evening dose (Dose 02): 01.00, 02.00, 03.00, 04.00, 05.00 hours | At Day 04: | Post-morning dose (Dose 07): 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, 12.00, 24.00, 48.00, and 72.00 hours. | Samples from Day 01 to Day 04 up to the 12.00-hour post-dose time point will be collected in-house at the study facility. | amples collected after the Post dose 07 at 24.00, 48.00 and 72.00 hours, will be collected on an ambulatory basis. All the ambulatory samples will be collected within 04.00 hour of the scheduled sampling time point
• Plasma levels of the primary active metabolite 7-hydroxy-cannabidiol
时间窗: 31 (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 Pre-morning Dose (within 05 minutes) | At Day 02 (within 05 minutes before Dose 03 and Dose 04) | At Day 03 (within 05 minutes before Dose 05 and Dose 06) | At Day 04 (within 05 minutes before Dose 07) | At Day 01: | Post-morning dose (Dose 01): 00.50, 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, and 12.00 hours (12.00 hours Post dose 01 Samples shall be collected within 5 minutes before Dose 02) | Post-evening dose (Dose 02): 01.00, 02.00, 03.00, 04.00, 05.00 hours | At Day 04: | Post-morning dose (Dose 07): 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 08.00, 12.00, 24.00, 48.00, and 72.00 hours. | Samples from Day 01 to Day 04 up to the 12.00-hour post-dose time point will be collected in-house at the study facility. | amples collected after the Post dose 07 at 24.00, 48.00 and 72.00 hours, will be collected on an ambulatory basis. All the ambulatory samples will be collected within 04.00 hour of the scheduled sampling time point
次要结局
- Secondary Outcome:(To evaluate the safety and tolerability of nano-encapsulated delayed-release cannabidiol tablets, including:)
研究者
Dr Shailender Singh Tanwar MBBS
BioRadius Therapeutic Research Pvt. Ltd.