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.
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
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- All
入选标准
- •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.
排除标准
- •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.
- •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.
- •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.
- •26.Unusual diet (e.g., low sodium) within 3 weeks before check-in.
- •28.Practicing a vegan diet.
- •29.Known hypersensitivity to cannabidiol or any EPIDIOLEX excipients.
- •For Female Volunteers Only:
- •Pregnant, lactating, planning pregnancy/gamete donation, or unwilling to use contraception during study and 3 weeks after.
- •Positive urine/serum pregnancy test during screening or before each period.
结局指标
主要结局
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
时间窗: 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
次要结局
- Safety and tolerability assessments, including:(Incidence and severity of adverse events (AEs))