Epilepsy, Partial Seizures With or Without Secondary Generalization
Conditions
Keywords
Epilepsy, Partial seizures with or without secondary generalization, Brivaracetam, Briviact
Brief summary
The purpose of the study is to evaluate the efficacy of brivaracetam (BRV) compared to placebo (PBO) as adjunctive treatment in subjects (\>=16 to 80 years of age) with partial seizures with or without secondary generalization despite current treatment with 1 or 2 concomitant antiepileptic drugs (AEDs) and to assess the safety and tolerability of BRV in subjects \>= 16 years to 80 years of age.
Interventions
DRUGPlacebo
* Pharmaceutical form: Film-coated tablets * Route of administration: Oral use
DRUGBrivaracetam
* Pharmaceutical form: Film-coated tablets * Concentration: 25 mg tablets and 50 mg tablets * Route of administration: Oral use
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects (male or female) from 16 to 80 years of age at Visit 1, both inclusive * Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method * Subjects having at least 8 partial seizures (according to the 1981 ILAE classification) during the 8-Week Baseline Period with at least 2 partial seizures during each 4-week interval of the Baseline Period * Subjects having at least 2 partial seizures whether or not secondary generalization per month during the 3 months preceding Visit 1 * Subjects uncontrolled while treated by 1 or 2 permitted concomitant antiepileptic drug \[AED\](s). Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED
Exclusion criteria
* Subject has history or presence of status epilepticus during the year preceding Visit 1 or during Baseline * Subject is currently treated with levetiracetam * Subject has taken levetiracetam within 90 days prior to Visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months) | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period. |
| Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal | From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months) | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period. |
| Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months) | Serious Adverse event (SAE) was defined as any events which: • results in death, • is life-threatening threatening (note that this did not include a reaction that might have caused death had it occurred in a more severe form.), •results in significant or persistent disability/incapacity, • results in a congenital anomaly/birth defect (including that occurring in a fetus), • results in Important medical event that, based upon appropriate medical judgment, may jeopardize the participant and might require medical or surgical intervention to prevent 1 of the other outcomes listed here, and • results in initial inpatient hospitalization or prolongation of hospitalization. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period. |
| Partial Seizure Frequency Per 28 Days During the 12-week Treatment Period | From Baseline to 12-week Treatment Period | According to International League Against Epilepsy (ILAE) classification (1981), seizures were classified as type IA (IA1, IA2, IA3, and IA4), IB, IC, II (IIA, IIB, IIC, IID, IIE, and IIF) or III. 28 day adjusted seizure frequency for partial seizures (seizure types IA+IB+IC) was calculated for treatment period by dividing the number of partial seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days During the 12-week Treatment Period | During the 12-week Treatment Period | There were three types of epileptic seizures: Partial epileptic seizures (Type I), Generalized epileptic seizures (Type II) and unclassified epileptic seizures (Type III). 28 day adjusted seizure frequency for all seizure types was calculated for treatment period by dividing the number of targeted seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28. |
| Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period | During the 12-week Treatment Period | Participants were defined as seizure free, if they did not have missing diary days and no reported seizures during the Treatment Period. |
| Time to 10th Partial Seizure During the 12-week Treatment Period | During the 12-week Treatment Period | The evaluation of time to 10th partial seizure was based on the relative day of occurrence of the 10th partial seizure during the Treatment Period. |
| Time to 5th Partial Seizure During the 12-week Treatment Period | During the 12-week Treatment Period | The evaluation of time to 5th partial seizure was based on the relative day of occurrence of the 5th partial seizure during the Treatment Period. |
| Brivaracetam Plasma Concentration | Plasma samples were collected at >0-4hours, >4-8hours, >8hours in weeks 2, 4, 8, 12, and 14 | Blood samples were collected at indicated time points for the 50mg/day and 200mg/day groups to determine the brivaracetam plasma concentration. Participants of arm 'BRV 200 mg/day' received BRV 200 mg/day until Week 12 only and 150 mg/day during the Transition Period at Week 14. Therefore, the data is reported according to the dosage information at specified time point. As per planned analysis, one blood sample was collected for BRV plasma levels during each dosing interval between 0 to 4 hours, 4 to 8 hours, and 8 to 12 hours postdose. |
| Time to 1st Partial Seizure During the 12-week Treatment Period | During the 12-week Treatment Period | The evaluation of time to 1st partial seizure was based on the relative day of occurrence of the 1st partial seizure during the Treatment Period. |
| 50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | From Baseline to 12-week Treatment Period | Responders were those participants with at least 50% reduction from Baseline to the 12-week Treatment Period in partial seizure frequency per 28 days. 50% Responder rate was calculated for treatment period by dividing the number of 50% responders by the number of participants in the analysis set and multiplying the resulting value by 100. |
| Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | From Baseline to 12-week Treatment Period | Percent change from Baseline to the Treatment Period in partial seizure frequency was calculated by subtracting 28-day adjusted Treatment Period partial seizure frequency from 28-day adjusted Baseline Period partial seizure frequency, and multiplying the resulting quantity by 100 and dividing by the Baseline Period 28-day adjusted partial seizure frequency. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline to the Treatment Period. |
| Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | From Baseline to 12-week Treatment Period | The percentage of participants within each of the following categories of percent change in partial seizure frequency from Baseline to the Treatment Period were summarized for each treatment group: 100%, 75% to less than 100%, 50% to less than 75%, 25% to less than 50%, -25% to less than 25%, and less than -25%. Percent change from Baseline to the Treatment Period in partial seizure frequency was calculated by subtracting 28-day adjusted Treatment Period partial seizure frequency from 28-day adjusted Baseline Period partial seizure frequency and multiplying the resulting quantity by 100 and dividing by the Baseline Period 28-day adjusted partial seizure frequency. |
Countries
China, Japan, Malaysia, Philippines, Singapore, Taiwan, Thailand
Participant flow
Recruitment details
The study started to enroll participants in August 2017 and concluded in June 2022.
Pre-assignment details
The Participant Flow refers to the Randomized Set. Double-Blind Period included Treatment Period and the Down-Titration Period plus Study Drug-Free Period or the Transition Period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching Placebo as film-coated tablets, administered orally, twice daily (bid), during 12 weeks of Treatment Period. At the end of the Treatment Period, participants who entered long-term follow-up (LTFU) study (EP0085 (NCT03250377)) or managed access program (MAP), the same matching Placebo dose was kept during 2 weeks of Transition Period and brivaracetam (BRV) 100 milligrams/day (mg/day) in LTFU study or MAP. Participants who did not enter the LTFU study or MAP had 4 weeks Down-Titration Period followed by a Study Drug-Free Period (no drug for 2 weeks). During Down-Titration Period, participants received the same Placebo dose for 4 weeks. | 149 |
| BRV 50 mg/Day Participants received BRV 50 mg/day as film-coated tablets, administered orally, bid, during 12 weeks of Treatment Period. At the end of the Treatment Period, participants who entered the LTFU study or MAP received BRV 50 mg/day during 2 weeks of Transition Period and BRV 100 mg/day in LTFU study or MAP. Participants who did not enter the LTFU study or MAP had 4 weeks Down-Titration Period followed by a Study Drug-Free Period (no drug for 2 weeks). During Down-Titration Period, participants received BRV 25 mg/day for 1 week followed by Placebo for 3 weeks. | 152 |
| BRV 200 mg/Day Participants received BRV 200 mg/day as film-coated tablets, administered orally, bid, during 12 weeks of Treatment Period. At the end of the Treatment Period, participants who entered LTFU study or MAP received BRV 150 mg/day during 2 weeks of Transition Period and BRV 100 mg/day in LTFU study or MAP. Participants who did not enter the LTFU study or MAP had 4 weeks Down-Titration Period followed by a Study Drug-Free Period (no drug for 2 weeks). During Down-Titration Period, participants received BRV 150 mg/day for 1 week followed by BRV 100 mg/day for 1 week, followed by BRV 50 mg/day for 1 week, followed by BRV 25 mg/day for 1 week. | 148 |
| Total | 449 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Double-Blind Period | Adverse Event | 5 | 4 | 5 | 0 | 0 | 0 |
| Double-Blind Period | Consent withdrawn by subject due to concern on AE | 1 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Period | Lack of Efficacy | 0 | 0 | 1 | 0 | 0 | 0 |
| Double-Blind Period | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 |
| Double-Blind Period | Protocol Violation | 1 | 0 | 1 | 0 | 0 | 0 |
| Double-Blind Period | Subjects were able to never take a study drug | 0 | 1 | 0 | 0 | 0 | 0 |
| Double-Blind Period | Withdrawal by Subject | 3 | 0 | 0 | 0 | 0 | 0 |
| Open-Label Temporary Period (OLTP) | Adverse Event | 0 | 0 | 0 | 2 | 0 | 0 |
| Open-Label Temporary Period (OLTP) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 2 |
| Open-Label Temporary Period (OLTP) | Patient non compliant to open label study drug | 0 | 0 | 0 | 0 | 0 | 1 |
| Open-Label Temporary Period (OLTP) | Patient not keen to continue open label | 0 | 0 | 0 | 1 | 0 | 0 |
| Open-Label Temporary Period (OLTP) | Subject enrolled to compassionate use program | 0 | 0 | 0 | 0 | 0 | 1 |
| Open-Label Temporary Period (OLTP) | Withdrawal by parent/guardian | 0 | 0 | 0 | 0 | 0 | 1 |
| Open-Label Temporary Period (OLTP) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | BRV 50 mg/Day | BRV 200 mg/Day | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 14 Participants | 8 Participants | 31 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 137 Participants | 135 Participants | 138 Participants | 410 Participants |
| Age, Continuous | 34.5 years STANDARD_DEVIATION 13.2 | 33.7 years STANDARD_DEVIATION 12.6 | 35.2 years STANDARD_DEVIATION 13.2 | 34.5 years STANDARD_DEVIATION 13 |
| Race/Ethnicity, Customized Asian | 149 Participants | 152 Participants | 148 Participants | 449 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 148 Participants | 151 Participants | 147 Participants | 446 Participants |
| Sex: Female, Male Female | 82 Participants | 77 Participants | 83 Participants | 242 Participants |
| Sex: Female, Male Male | 67 Participants | 75 Participants | 65 Participants | 207 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 149 | 1 / 151 | 0 / 148 | 0 / 64 | 0 / 68 | 0 / 74 |
| other Total, other adverse events | 39 / 149 | 42 / 151 | 54 / 148 | 3 / 64 | 4 / 68 | 4 / 74 |
| serious Total, serious adverse events | 1 / 149 | 2 / 151 | 4 / 148 | 3 / 64 | 0 / 68 | 2 / 74 |
Outcome results
Primary
Partial Seizure Frequency Per 28 Days During the 12-week Treatment Period
According to International League Against Epilepsy (ILAE) classification (1981), seizures were classified as type IA (IA1, IA2, IA3, and IA4), IB, IC, II (IIA, IIB, IIC, IID, IIE, and IIF) or III. 28 day adjusted seizure frequency for partial seizures (seizure types IA+IB+IC) was calculated for treatment period by dividing the number of partial seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28.
Time frame: From Baseline to 12-week Treatment Period
Population: The Full Analysis Set (FAS) consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure daily record card (DRC) data during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Partial Seizure Frequency Per 28 Days During the 12-week Treatment Period | 7.17 seizures per 28 days |
| BRV 50 mg/Day | Partial Seizure Frequency Per 28 Days During the 12-week Treatment Period | 5.93 seizures per 28 days |
| BRV 200 mg/Day | Partial Seizure Frequency Per 28 Days During the 12-week Treatment Period | 4.19 seizures per 28 days |
p-value: 0.000595% CI: [11.7, 35.5]ANCOVA
p-value: <0.000195% CI: [21.9, 43.1]ANCOVA
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Time frame: From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months)
Population: The Safety Set (SS) included all randomized study participants who received at least 1 dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 58.4 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 57.0 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 60.1 percentage of participants |
| Placebo to OLTP BRV | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 26.6 percentage of participants |
| BRV 50 mg/Day to OLTP BRV | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 19.1 percentage of participants |
| BRV 200 mg/Day to OLTP BRV | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 23.0 percentage of participants |
Primary
Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Time frame: From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months)
Population: The SS included all randomized study participants who received at least 1 dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal | 4.7 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal | 2.6 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal | 3.4 percentage of participants |
| Placebo to OLTP BRV | Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal | 0 percentage of participants |
| BRV 50 mg/Day to OLTP BRV | Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal | 0 percentage of participants |
| BRV 200 mg/Day to OLTP BRV | Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal | 0 percentage of participants |
Primary
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Serious Adverse event (SAE) was defined as any events which: • results in death, • is life-threatening threatening (note that this did not include a reaction that might have caused death had it occurred in a more severe form.), •results in significant or persistent disability/incapacity, • results in a congenital anomaly/birth defect (including that occurring in a fetus), • results in Important medical event that, based upon appropriate medical judgment, may jeopardize the participant and might require medical or surgical intervention to prevent 1 of the other outcomes listed here, and • results in initial inpatient hospitalization or prolongation of hospitalization. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Time frame: From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months)
Population: The SS included all randomized study participants who received at least 1 dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | 0.7 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | 1.3 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | 2.7 percentage of participants |
| Placebo to OLTP BRV | Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | 4.7 percentage of participants |
| BRV 50 mg/Day to OLTP BRV | Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | 0 percentage of participants |
| BRV 200 mg/Day to OLTP BRV | Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | 2.7 percentage of participants |
Secondary
50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period
Responders were those participants with at least 50% reduction from Baseline to the 12-week Treatment Period in partial seizure frequency per 28 days. 50% Responder rate was calculated for treatment period by dividing the number of 50% responders by the number of participants in the analysis set and multiplying the resulting value by 100.
Time frame: From Baseline to 12-week Treatment Period
Population: The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 19.0 percentage of responders |
| BRV 50 mg/Day | 50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 41.1 percentage of responders |
| BRV 200 mg/Day | 50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 49.3 percentage of responders |
Secondary
All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days During the 12-week Treatment Period
There were three types of epileptic seizures: Partial epileptic seizures (Type I), Generalized epileptic seizures (Type II) and unclassified epileptic seizures (Type III). 28 day adjusted seizure frequency for all seizure types was calculated for treatment period by dividing the number of targeted seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28.
Time frame: During the 12-week Treatment Period
Population: The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days During the 12-week Treatment Period | 7.17 seizures per 28 days |
| BRV 50 mg/Day | All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days During the 12-week Treatment Period | 5.93 seizures per 28 days |
| BRV 200 mg/Day | All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days During the 12-week Treatment Period | 4.19 seizures per 28 days |
Secondary
Brivaracetam Plasma Concentration
Blood samples were collected at indicated time points for the 50mg/day and 200mg/day groups to determine the brivaracetam plasma concentration. Participants of arm 'BRV 200 mg/day' received BRV 200 mg/day until Week 12 only and 150 mg/day during the Transition Period at Week 14. Therefore, the data is reported according to the dosage information at specified time point. As per planned analysis, one blood sample was collected for BRV plasma levels during each dosing interval between 0 to 4 hours, 4 to 8 hours, and 8 to 12 hours postdose.
Time frame: Plasma samples were collected at >0-4hours, >4-8hours, >8hours in weeks 2, 4, 8, 12, and 14
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all study participants who took at least 1 dose of BRV and for whom at least 1 valid BRV plasma concentration time and dosing information were available. Here, 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Brivaracetam Plasma Concentration | Week 2: > 0 - 4 hours | 0.68556 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 95.6 |
| Placebo | Brivaracetam Plasma Concentration | Week 8: > 8 hours | 0.27840 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 10.9 |
| Placebo | Brivaracetam Plasma Concentration | Week 4: > 4 - 8 hours | 0.64781 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 39.2 |
| Placebo | Brivaracetam Plasma Concentration | Week 12: > 0 - 4 hours | 0.77400 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 89.5 |
| Placebo | Brivaracetam Plasma Concentration | Week 2: > 4 - 8 hours | 0.66523 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 38.6 |
| Placebo | Brivaracetam Plasma Concentration | Week 12: > 4 - 8 hours | 0.65274 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 39.4 |
| Placebo | Brivaracetam Plasma Concentration | Week 4: > 8 hours | 0.39652 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 54.7 |
| Placebo | Brivaracetam Plasma Concentration | Week 12: > 8 hours | 0.18229 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 579.5 |
| Placebo | Brivaracetam Plasma Concentration | Week 4: > 0 - 4 hours | 0.75902 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 88.8 |
| Placebo | Brivaracetam Plasma Concentration | Week 14 (Transition): > 0 - 4 hours | 0.75949 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 85.3 |
| Placebo | Brivaracetam Plasma Concentration | Week 14 (Transition): > 8 hours | 0.41286 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 66.4 |
| Placebo | Brivaracetam Plasma Concentration | Week 14 (Transition): > 4 - 8 hours | 0.75692 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 34.6 |
| Placebo | Brivaracetam Plasma Concentration | Week 8: > 0 - 4 hours | 0.76942 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 87.3 |
| Placebo | Brivaracetam Plasma Concentration | Week 2: > 8 hours | 0.18427 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 979.4 |
| Placebo | Brivaracetam Plasma Concentration | Week 8: > 4 - 8 hours | 0.76172 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 34 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 8: > 4 - 8 hours | 2.7030 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 54.9 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 2: > 0 - 4 hours | 3.4340 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 42.5 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 2: > 4 - 8 hours | 2.0615 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 334.4 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 2: > 8 hours | 1.2144 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 100.1 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 4: > 0 - 4 hours | 3.0038 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 120.2 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 4: > 4 - 8 hours | 2.8516 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 43.2 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 4: > 8 hours | 1.1054 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 74.4 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 8: > 0 - 4 hours | 2.9983 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 127.7 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 8: > 8 hours | 1.5590 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 67.7 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 12: > 0 - 4 hours | 3.2508 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 121.1 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 12: > 4 - 8 hours | 1.6017 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 838.9 |
| BRV 50 mg/Day | Brivaracetam Plasma Concentration | Week 12: > 8 hours | 1.5001 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 45.4 |
| BRV 200 mg/Day | Brivaracetam Plasma Concentration | Week 14 (Transition): > 4 - 8 hours | 1.4383 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 309.5 |
| BRV 200 mg/Day | Brivaracetam Plasma Concentration | Week 14 (Transition): > 0 - 4 hours | 2.4989 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 54.8 |
| BRV 200 mg/Day | Brivaracetam Plasma Concentration | Week 14 (Transition): > 8 hours | 0.82681 microgram/ millilitre (ug/mL) | Geometric Coefficient of Variation 30.6 |
Secondary
Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period
Participants were defined as seizure free, if they did not have missing diary days and no reported seizures during the Treatment Period.
Time frame: During the 12-week Treatment Period
Population: The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period | All epileptic seizures | 0 percentage of participants |
| Placebo | Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period | Partial onset seizures | 0 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period | All epileptic seizures | 4.6 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period | Partial onset seizures | 4.6 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period | All epileptic seizures | 6.8 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period | Partial onset seizures | 6.8 percentage of participants |
Secondary
Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period
The percentage of participants within each of the following categories of percent change in partial seizure frequency from Baseline to the Treatment Period were summarized for each treatment group: 100%, 75% to less than 100%, 50% to less than 75%, 25% to less than 50%, -25% to less than 25%, and less than -25%. Percent change from Baseline to the Treatment Period in partial seizure frequency was calculated by subtracting 28-day adjusted Treatment Period partial seizure frequency from 28-day adjusted Baseline Period partial seizure frequency and multiplying the resulting quantity by 100 and dividing by the Baseline Period 28-day adjusted partial seizure frequency.
Time frame: From Baseline to 12-week Treatment Period
Population: The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 100% | 0 percentage of participants |
| Placebo | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 75% to less than 100% | 3.4 percentage of participants |
| Placebo | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 50% to less than 75% | 15.6 percentage of participants |
| Placebo | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 25% to less than 50% | 27.2 percentage of participants |
| Placebo | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | -25% to less than 25% | 42.9 percentage of participants |
| Placebo | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | less than-25% | 10.9 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | less than-25% | 11.3 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 100% | 5.3 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 25% to less than 50% | 16.6 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | -25% to less than 25% | 31.1 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 75% to less than 100% | 14.6 percentage of participants |
| BRV 50 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 50% to less than 75% | 21.2 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 75% to less than 100% | 17.6 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 50% to less than 75% | 24.3 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | less than-25% | 11.5 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 25% to less than 50% | 20.9 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 100% | 7.4 percentage of participants |
| BRV 200 mg/Day | Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | -25% to less than 25% | 18.2 percentage of participants |
Secondary
Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period
Percent change from Baseline to the Treatment Period in partial seizure frequency was calculated by subtracting 28-day adjusted Treatment Period partial seizure frequency from 28-day adjusted Baseline Period partial seizure frequency, and multiplying the resulting quantity by 100 and dividing by the Baseline Period 28-day adjusted partial seizure frequency. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline to the Treatment Period.
Time frame: From Baseline to 12-week Treatment Period
Population: The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 21.3 percent change |
| BRV 50 mg/Day | Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 38.9 percent change |
| BRV 200 mg/Day | Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period | 46.7 percent change |
Secondary
Time to 10th Partial Seizure During the 12-week Treatment Period
The evaluation of time to 10th partial seizure was based on the relative day of occurrence of the 10th partial seizure during the Treatment Period.
Time frame: During the 12-week Treatment Period
Population: The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to 10th Partial Seizure During the 12-week Treatment Period | 43 days |
| BRV 50 mg/Day | Time to 10th Partial Seizure During the 12-week Treatment Period | 59 days |
| BRV 200 mg/Day | Time to 10th Partial Seizure During the 12-week Treatment Period | 69 days |
Secondary
Time to 1st Partial Seizure During the 12-week Treatment Period
The evaluation of time to 1st partial seizure was based on the relative day of occurrence of the 1st partial seizure during the Treatment Period.
Time frame: During the 12-week Treatment Period
Population: The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to 1st Partial Seizure During the 12-week Treatment Period | 3 days |
| BRV 50 mg/Day | Time to 1st Partial Seizure During the 12-week Treatment Period | 5 days |
| BRV 200 mg/Day | Time to 1st Partial Seizure During the 12-week Treatment Period | 6 days |
Secondary
Time to 5th Partial Seizure During the 12-week Treatment Period
The evaluation of time to 5th partial seizure was based on the relative day of occurrence of the 5th partial seizure during the Treatment Period.
Time frame: During the 12-week Treatment Period
Population: The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to 5th Partial Seizure During the 12-week Treatment Period | 17 days |
| BRV 50 mg/Day | Time to 5th Partial Seizure During the 12-week Treatment Period | 28 days |
| BRV 200 mg/Day | Time to 5th Partial Seizure During the 12-week Treatment Period | 32 days |