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 dry syrup after multiple oral doses in healthy male Japanese participants.
Interventions
DRUGbrivaracetam (BRV) tablet
Study participants will receive multiple-doses of brivaracetam tablet (reference - Treatment A) administered orally.
DRUGbrivaracetam (BRV) dry syrup
Study participants will receive multiple-doses of brivaracetam dry syrup (test - Treatment B) 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
* Participant must be between 20 to 50 years of age (inclusive) at the time of signing the informed consent form (ICF) * Participant is of Japanese descent as evidenced by appearance and verbal confirmation of familial heritage (ie, participant has all 4 Japanese grandparents born in Japan) * Participant is male
Exclusion criteria
* Participant has a known hypersensitivity to any components of the investigational medicinal product (IMP) formulations * Participant has participated in another study of an IMP (and/or an investigational device) within the previous 30 days or within 5 times the half-life (whichever is longer) of the first dose of BRV in this study or is currently participating in another study of an IMP (and/or an investigational device) * Participant tests positive for alcohol and/or prohibited concomitant drugs (including cotinine) at the Screening Visit or on Day-1 * 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 * Participant is a current smoker or has used nicotine-containing products (eg, tobacco, patches, gum) within 30 days before the first administration of IMP
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration at Steady State [Cmax(ss)] After Multiple Doses of Brivaracetam | Day 1: before the morning and evening doses (0 and 12 hr); Day 2: before the morning and evening doses (24 and 36 hr); Day 3: Predose (48 hr) and 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 75 min, 90 min, 2 hr, 6 hr, 9 hr, and 12 hr postdose | Cmax,ss is the maximum plasma concentration of brivaracetam at steady state. |
| Area Under the Curve During a Dosing Interval at Steady State [AUC(Tau)] After Multiple Doses of Brivaracetam | Day 1: before the morning and evening doses (0 and 12 hr); Day 2: before the morning and evening doses (24 and 36 hr); Day 3: Predose (48 hr) and 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 75 min, 90 min, 2 hr, 6 hr, 9 hr, and 12 hr postdose | AUCtau was area under the curve during a dosing interval at steady state of brivaracetam. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Study Participants With Treatment-emergent Adverse Events (TEAEs) | From Baseline to end of Safety Follow-up (up to 25 days) | An AE was 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 Study Participants With Treatment-emergent Serious Adverse Events (TESAEs) | From Baseline to end of Safety Follow-up (up to 25 days) | 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. 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, Results in persistent disability/incapacity 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. |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation | From Baseline to end of Safety Follow-up (up to 25 days) | Percentage of participants with TEAEs leading to discontinuation were reported. |
Countries
Japan
Participant flow
Recruitment details
The study started to enroll participants in March 2024 and concluded in June 2024.
Pre-assignment details
The Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| Sequence Brivaracetam (BRV) Tablet - BRV Dry Syrup Dosing period 1 consisted of 5 days (Day -1 \[1 day before administration of IMP\] to Day 4): On Day 1 and Day 2 each participant received a dose of BRV 50 mg tablet formulation twice daily; on Day 3, each participant received a single morning dose of BRV 50 mg tablet formulation. Dosing period 2 consisted of 5 days (Day -1 \[1 day before administration of IMP\] to Day 4): On Day 1 and Day 2 each participant received a dose of BRV 50mg as dry syrup twice daily; on Day 3, each participant received a single morning dose of BRV 50 mg as dry syrup. The final IMP administration in Dosing Period 1 and the first investigational medicinal product (IMP) administration in Dosing Period 2 were separated by a washout period of 6-10 days. | 32 |
| Sequence BRV Dry Syrup - BRV Tablet Dosing period 1 consisted of 5 days (Day -1 \[1 day before administration of IMP\] to Day 4): on Day 1 and Day 2 each participant received a dose of BRV 50 mg as dry syrup twice daily. On Day 3, each participant received a single morning dose of BRV 50 mg as dry syrup. Dosing period 2 consisted of 5 days (Day -1 \[1 day before administration of IMP\] to Day 4): On Day 1 and Day 2 each participant received a dose of BRV 50 mg tablet formulation twice daily; on Day 3 of Dosing Period 2, each participant received a single morning dose of BRV 50 mg tablet formulation. The final IMP administration in Dosing Period 1 and the first IMP administration in Dosing Period 2 were separated by a washout period of 6-10 days. | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Sequence Brivaracetam (BRV) Tablet - BRV Dry Syrup | Sequence BRV Dry Syrup - BRV Tablet | Total |
|---|---|---|---|
| Age, Continuous | 33.5 years STANDARD_DEVIATION 9.8 | 33.8 years STANDARD_DEVIATION 9.1 | 33.6 years STANDARD_DEVIATION 9.4 |
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 19 - 65 years | 32 Participants | 32 Participants | 64 Participants |
| Age, Customized >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 32 Participants | 32 Participants | 64 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 32 Participants | 32 Participants | 64 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 32 Participants | 32 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 64 |
| other Total, other adverse events | 2 / 63 | 6 / 64 |
| serious Total, serious adverse events | 0 / 63 | 0 / 64 |
Outcome results
Primary
Area Under the Curve During a Dosing Interval at Steady State [AUC(Tau)] After Multiple Doses of Brivaracetam
AUCtau was area under the curve during a dosing interval at steady state of brivaracetam.
Time frame: Day 1: before the morning and evening doses (0 and 12 hr); Day 2: before the morning and evening doses (24 and 36 hr); Day 3: Predose (48 hr) and 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 75 min, 90 min, 2 hr, 6 hr, 9 hr, and 12 hr postdose
Population: PK set included all participants who were randomized, received at least 1 dose of active IMP, and had at least 1 quantifiable post-Baseline PK measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BRV Tablet | Area Under the Curve During a Dosing Interval at Steady State [AUC(Tau)] After Multiple Doses of Brivaracetam | 18.55 hours*μg/mL | Geometric Coefficient of Variation 17.4 |
| BRV Dry Syrup | Area Under the Curve During a Dosing Interval at Steady State [AUC(Tau)] After Multiple Doses of Brivaracetam | 18.53 hours*μg/mL | Geometric Coefficient of Variation 16.8 |
92.016% CI: [0.9881, 1.012]
Primary
Maximum Plasma Concentration at Steady State [Cmax(ss)] After Multiple Doses of Brivaracetam
Cmax,ss is the maximum plasma concentration of brivaracetam at steady state.
Time frame: Day 1: before the morning and evening doses (0 and 12 hr); Day 2: before the morning and evening doses (24 and 36 hr); Day 3: Predose (48 hr) and 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 75 min, 90 min, 2 hr, 6 hr, 9 hr, and 12 hr postdose
Population: Pharmacokinetic (PK) set included all participants who were randomized, received at least 1 dose of active IMP, and had at least 1 quantifiable post-baseline PK measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BRV Tablet | Maximum Plasma Concentration at Steady State [Cmax(ss)] After Multiple Doses of Brivaracetam | 2.963 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 24.1 |
| BRV Dry Syrup | Maximum Plasma Concentration at Steady State [Cmax(ss)] After Multiple Doses of Brivaracetam | 2.878 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 19.5 |
92.016% CI: [0.9257, 1.022]Linear mixed model analysis
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation
Percentage of participants with TEAEs leading to discontinuation were reported.
Time frame: From Baseline to end of Safety Follow-up (up to 25 days)
Population: SS included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BRV Tablet | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation | 0 percentage of participants |
| BRV Dry Syrup | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation | 0 percentage of participants |
Secondary
Percentage of Study Participants With Treatment-emergent Adverse Events (TEAEs)
An AE was 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 25 days)
Population: SS included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BRV Tablet | Percentage of Study Participants With Treatment-emergent Adverse Events (TEAEs) | 4.8 percentage of participants |
| BRV Dry Syrup | Percentage of Study Participants With Treatment-emergent Adverse Events (TEAEs) | 10.9 percentage of participants |
Secondary
Percentage of Study Participants With Treatment-emergent Serious Adverse Events (TESAEs)
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. 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, Results in persistent disability/incapacity 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 25 days)
Population: SS included all randomized participants who received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BRV Tablet | Percentage of Study Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 0 percentage of participants |
| BRV Dry Syrup | Percentage of Study Participants With Treatment-emergent Serious Adverse Events (TESAEs) | 0 percentage of participants |