Healthy Study Participants
Conditions
Keywords
brivaracetam, Healthy Study Participants, Phase 1, BRV
Brief summary
The purpose of the study is to demonstrate the bioequivalence between the BRV tablet and BRV as dry syrup after a single oral dose in healthy Japanese male study participants.
Interventions
DRUGbrivaracetam
Study participants will receive a single-dose of brivaractam tablet (reference - Treatment A) administered orally.
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Study participant must be between 20 to 50 years of age (inclusive) at the time of signing the Informed Consent Form (ICF) * Study participant is overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring * Study participant is of Japanese descent as evidenced by appearance and verbal confirmation of familial heritage (a study participant has all 4 Japanese grandparents born in Japan)
Exclusion criteria
* Study participant has used other drugs, including over-the-counter medications, herbal/traditional medicines, or dietary supplements (excluding medicines for external use),with the exception of paracetamol, within 14 days before first administration of IMP or has received a coronavirus disease 2019 (COVID-19) vaccine within 7 days of initiating IMP * Study participant has used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, isoniazid, phenytoin, rifampicin) within 2 months before the first administration of Investigational Medicinal Product (IMP) * Study participant has a positive result for hepatitis B surface antigen, hepatitis C virus antibody test, human immunodeficiency virus antibody test, or syphilis at Screening Visit * Study participant has donated blood or plasma or has experienced blood loss ≥400 mL within 90 days, ≥200 mL within 30 days, or has donated any blood or plasma within 14 days before first administration of IMP * Study participant is a current smoker or has used nicotine-containing products (eg, tobacco, patches, gum) within 30 days before the first administration of IMP * Consumption of more than 600 mg of caffeine/day (1 cup of coffee contains approximately 100mg of caffeine, 1 cup of tea approximately 30 mg, and 1 glass of cola approximately 20 mg)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) for a Single Dose of Brivaracetam | Blood samples for this analysis were collected on Predose (Day 1), 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | Cmax is the maximum plasma concentration of brivaracetam. |
| Area Under the Curve From 0 to the Time of the Last Quantifiable Concentration (AUC(0-t)) for a Single Dose of Brivaracetam | Blood samples for this analysis were collected on Predose (Day 1), 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose | AUC(0-t) is the area under the curve from time 0 to the time of the last quantifiable concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | From Baseline to end of Safety Follow-Up, up to 20 days | An AE was defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. A TEAE was defined as any AE with a start date/time on or after the first dose of IMP or any unresolved event already present before administration of IMP that worsens in intensity following exposure to IMP. |
| Percentage of Participants With at Least One Treatment-emergent Serious Adverse Event (SAE) | From Baseline to end of Safety Follow-Up, up to 20 days | A TEAE was any AE with a start date/time on or after the first dose of IMP or any unresolved event already present before administration of IMP that worsens in intensity following exposure to IMP. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, Is life-threatening, Requires in patient hospitalization or prolongation of existing hospitalization,Is a congenital anomaly or birth defect, Is an infection that requires treatment parenteral antibiotics, Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. |
Countries
Japan
Participant flow
Recruitment details
The study started to enroll participants in April 2022 and concluded in May 2022.
Pre-assignment details
The Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| BRV (All Participants) All participants received a single dose of either BRV 50 mg tablet or BRV 50 mg as dry syrup, orally, in the morning under fasting conditions on Day 1 of Dosing Period 1. After a washout period of 7 to 10 days, all participants received a single dose of either BRV 50 mg tablet or BRV 50 mg as dry syrup, orally, in the morning under fasting conditions on Day 1 of Dosing Period 2. Each dosing period is of 4 days, with a single administration on Day 1 of Dosing Period. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | BRV (All Participants) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 34.5 years STANDARD_DEVIATION 8.7 |
| Race/Ethnicity, Customized Asian | 24 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 24 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 9 / 24 | 8 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Area Under the Curve From 0 to the Time of the Last Quantifiable Concentration (AUC(0-t)) for a Single Dose of Brivaracetam
AUC(0-t) is the area under the curve from time 0 to the time of the last quantifiable concentration.
Time frame: Blood samples for this analysis were collected on Predose (Day 1), 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
Population: Pharmacokinetic Per Protocol Set (PK-PPS) included all randomized study participants who were included in the SS, had no important protocol deviations (IPDs) that were considered to impact the data validity for analysis of the primary study objective, and had a sufficient number of bioanalytical assessments to calculate reliable estimates for the primary pharmacokinetic parameters for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BRV Tablet | Area Under the Curve From 0 to the Time of the Last Quantifiable Concentration (AUC(0-t)) for a Single Dose of Brivaracetam | 17.98 hours*μg/mL | Geometric Coefficient of Variation 17 |
| BRV Dry Syrup | Area Under the Curve From 0 to the Time of the Last Quantifiable Concentration (AUC(0-t)) for a Single Dose of Brivaracetam | 17.78 hours*μg/mL | Geometric Coefficient of Variation 16.2 |
90% CI: [0.9756, 1.003]
Primary
Maximum Plasma Concentration (Cmax) for a Single Dose of Brivaracetam
Cmax is the maximum plasma concentration of brivaracetam.
Time frame: Blood samples for this analysis were collected on Predose (Day 1), 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
Population: Pharmacokinetic Per Protocol Set (PK-PPS) included all randomized study participants who were included in the SS, had no important protocol deviations (IPDs) that were considered to impact the data validity for analysis of the primary study objective, and had a sufficient number of bioanalytical assessments to calculate reliable estimates for the primary pharmacokinetic parameters for both treatments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BRV Tablet | Maximum Plasma Concentration (Cmax) for a Single Dose of Brivaracetam | 2.286 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 24.5 |
| BRV Dry Syrup | Maximum Plasma Concentration (Cmax) for a Single Dose of Brivaracetam | 1.989 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 22.4 |
90% CI: [0.7814, 0.9686]
Secondary
Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
An AE was defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. A TEAE was defined as any AE with a start date/time on or after the first dose of IMP or any unresolved event already present before administration of IMP that worsens in intensity following exposure to IMP.
Time frame: From Baseline to end of Safety Follow-Up, up to 20 days
Population: Safety Set (SS) included all randomized study participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BRV Tablet | Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | 37.5 percentage of participants |
| BRV Dry Syrup | Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE) | 37.5 percentage of participants |
Secondary
Percentage of Participants With at Least One Treatment-emergent Serious Adverse Event (SAE)
A TEAE was any AE with a start date/time on or after the first dose of IMP or any unresolved event already present before administration of IMP that worsens in intensity following exposure to IMP. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, Is life-threatening, Requires in patient hospitalization or prolongation of existing hospitalization,Is a congenital anomaly or birth defect, Is an infection that requires treatment parenteral antibiotics, Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.
Time frame: From Baseline to end of Safety Follow-Up, up to 20 days
Population: Safety Set (SS) included all randomized study participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BRV Tablet | Percentage of Participants With at Least One Treatment-emergent Serious Adverse Event (SAE) | 0 percentage of participants |
| BRV Dry Syrup | Percentage of Participants With at Least One Treatment-emergent Serious Adverse Event (SAE) | 0 percentage of participants |