Epilepsy (treatment Refractory)
Conditions
Keywords
crossover, bioequivalence, Brivaracetam Oral Solution
Brief summary
The goal of this clinical trial is to evaluate the bioequivalence of Brivaracetam oral solution under fasting and high-fat meal conditions in healthy adults. The study will compare a test formulation (produced by Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd., 300ml: 3g) to the reference formulation (Briviact®, UCB Pharma S.A., 300ml: 3g). The main questions it aims to answer are: 1. Do the test and reference formulations of Brivaracetam oral solution exhibit similar pharmacokinetic behavior in the body? 2. What are the clinical safety outcomes for participants taking the test and reference formulations? Participants will: Be randomly assigned to two treatment sequences (T-R or R-T) in a 1:1 ratio. Receive either the test formulation or reference formulation of Brivaracetam oral solution (10ml), taken with 240mL of warm water, under either fasting or high-fat meal conditions. Cross over to the alternate formulation after a 7-day washout period, completing a total of two treatment periods (2 weeks). Undergo regular checkups and tests to monitor pharmacokinetics and safety outcomes.
Interventions
DRUGBrivaracetam Oral Solution (Test Formulation)
The drug is manufactured by Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd. The formulation is provided as a 300 mL: 3 g solution, with a dosage of 10 mL (100 mg) per single oral dose. The drug will be administered to participants in the fasting group during the first phase of the study and to participants in the high-fat meal group during the second phase of the study.
DRUGBrivaracetam Oral Solution (Reference Formulation)
The drug is manufactured by UCB Pharma S.A. under the trade name Briviact®. The formulation is provided as a 300 mL: 3 g solution, with a dosage of 10 mL (100 mg) per single oral dose. The drug will be administered to participants in the fasting group during the first phase of the study and to participants in the high-fat meal group during the second phase of the study.
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Masking description
This is an open-label study; all participants and investigators are aware of the treatment assignments.
Intervention model description
A two-period, two-sequence crossover design where participants are randomly assigned to receive either the test or reference formulation in a fasted or fed state, with a washout period of seven days between treatments.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Age and Gender: Healthy male and female participants aged 18-55 years (inclusive). * Weight and BMI: Male participants must weigh ≥50 kg, and females ≥45 kg, with a body mass index (BMI) between 19 and 26. BMI is calculated as: BMI = weight (kg) / height (m²). * Participants must fully understand the purpose, methods, content, and test drugs of this study before enrollment, be capable of good communication with investigators, adhere to study requirements, and voluntarily sign the informed consent form. * Participants must commit to avoiding pregnancy and refraining from sperm/egg donation from the time of consent through 3 months after the last dose. Participants must agree to use effective contraception (non-pharmacological methods) during the trial. Female participants must have had no unprotected sexual activity within 14 days before the first dose.
Exclusion criteria
* History of allergies (e.g., angioedema, anaphylactic shock) or hypersensitivity (e.g., to pollen, two or more drugs/foods), or known allergy to briciclib or its excipients. * Past or current illnesses that may affect drug absorption, distribution, metabolism, excretion, or the interpretation of safety data, or conditions reducing compliance, including but not limited to gastrointestinal, renal, hepatic, pulmonary, neurological, hematological, endocrine, oncological, immunological, psychiatric, or cardiovascular diseases, as judged by the investigator. * Major surgery within 3 months prior to screening or planned surgery during the study period, including procedures affecting pharmacokinetics (e.g., gallbladder/biliary tract surgery). * History of significant bleeding, active bleeding, thrombocytopenia, coagulation disorders, or family history of coagulopathy. * Vaccination within 28 days prior to screening or planned vaccination during the study. * History of substance abuse or dependence within the past 5 years or use of drugs such as morphine, methamphetamine, ketamine, cannabis, or ecstasy within 6 months before screening. Positive urine drug screen results are also exclusionary. * Difficulty with venipuncture, intolerance to venous puncture, or history of needle or blood phobia. * Lactose intolerance. * Special dietary requirements that cannot align with standardized study diets. * Participation in any clinical trial and drug administration within 3 months prior to screening. * Blood donation or significant blood loss (≥400 mL) within 3 months prior to screening (excluding physiological blood loss in women) or intention to donate blood during the study. * Regular smokers (≥5 cigarettes/day) or habitual betel nut chewers within 3 months prior to screening, or inability to abstain from tobacco products during the study. * Frequent alcohol consumption (more than 14 units per week, where 1 unit = 360 mL beer, 45 mL spirits, or 150 mL wine) within 3 months prior to screening, positive breath alcohol test, or inability to abstain from alcohol during the study. * Excessive intake of tea, coffee, caffeine-containing products, grapefruit, or xanthine-rich foods or beverages (e.g., theophylline, caffeine, theobromine) averaging more than 8 cups/day (1 cup = 200 mL) within 3 months prior to screening or inability to discontinue such intake during the study. * Use of any medications, including prescription, over-the-counter drugs, herbal medicines, or health supplements, within 14 days prior to the first dose. * Use of any liver enzyme-altering drugs within 28 days prior to the first dose. * Pregnant or lactating women, or females with positive pregnancy tests. * Positive results for any of the following virological tests: Hepatitis B surface antigen, Hepatitis C antibody, HIV antibody, or syphilis antibody. * Clinically significant abnormalities in physical examination, vital signs, 12-lead ECG, or laboratory tests at screening, as determined by the investigator. * Other reasons that may prevent the participant from completing the study, or any other factors deemed unsuitable for participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | two weeks | Cmax is the maximum observed plasma concentration of the drug following a single oral dose. This parameter reflects the peak exposure to the drug in the bloodstream after administration. |
| Area Under the Plasma Concentration-Time Curve from Time 0 to Last Measurable Concentration (AUC0-t) | two weeks | AUC0-t represents the total drug exposure from time 0 to the last measurable concentration. It is an important pharmacokinetic parameter for understanding the extent of drug absorption over time. |
| Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) | two weeks | AUC0-∞ is the area under the plasma concentration-time curve from time 0 to infinity, capturing the total exposure to the drug. It includes all measurable concentrations, both during and after the absorption phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Plasma Concentration(Tmax ) | two weeks | Tmax is the time it takes to reach the maximum plasma concentration (Cmax) after a single dose of the drug. It indicates the rate at which the drug is absorbed into the bloodstream. |
| Percentage of the Area Under the Curve Extrapolated to Infinity(AUC_%Extrap ) | two weeks | AUC\_%Extrap is the percentage of the total AUC that is extrapolated beyond the last measured concentration (AUC∞ - AUC0-t) / AUC∞. This indicates the reliability of the AUC data and how much data is based on extrapolated values. |
| Terminal Elimination Rate Constant (λz) | two weeks | λz is the terminal elimination rate constant, which is used to describe the rate at which the drug is cleared from the body during the elimination phase. This value helps estimate the half-life of the drug. |
| Half-life (t1/2) | two weeks | t1/2 is the time required for the plasma concentration of the drug to decrease by half. It is a key pharmacokinetic parameter to understand the duration of action of the drug. |
Countries
China
Outcome results
None listed