Epilepsy, Partial Seizures With or Without Secondary Generalization
Conditions
Keywords
Brivaracetam, Epilepsy, Partial seizures with or without secondary generalization, Briviact
Brief summary
The purpose of the study is to evaluate the long-term safety and tolerability of Brivaracetam (BRV) in focal epilepsy subjects with partial seizures and to evaluate the maintenance of efficacy of BRV over time.
Interventions
DRUGBrivaracetam
* Pharmaceutical form: Film-coated tablet * Concentration: 25 mg and 50 mg * Route of administration: Oral use
Sponsors
UCB Biopharma SRL
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male/female study participant from 16 years of age or older. Study participant who are not legal adults may only be included where legally permitted and ethically accepted * Study participant completed the Treatment Period and Transition Period of EP0083 or is ongoing in N01379 sites in Japan * Female study participants with childbearing potential are eligible if they use a medically accepted contraceptive method * Inclusion Criteria for directly enrollers only: Study participant has 1 to \<8 partial seizures (according to the 1981 International League Against Epilepsy (ILAE) classification) during the 8 weeks prior to brivaracetam (BRV) administration
Exclusion criteria
* Study participant has developed hypersensitivity to any components of the investigational medicinal product (IMP) or comparative drugs as stated in this protocol during the course of the core study * Severe medical, neurological or psychiatric disorders, or laboratory values which may have an impact on the safety of the study participant * Poor compliance with the visit schedule or medication intake in the previous BRV studies * Planned participation in any other clinical study of another investigational drug or device during this study * Pregnant or lactating woman * Any medical condition which, in the Investigator's opinion, warrants exclusion * Study participant has a lifetime history of suicide attempt or has suicidal ideation in the past 6 months * Study participant has \>2 x upper limit of normal (ULN) of any of the following at the Entry Visit (EV): alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or \>ULN total bilirubin (≥1.5x ULN total bilirubin if known Gilbert's syndrome)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | From Baseline until end of the safety follow up (up to 88.5 months) | An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent AEs (TEAEs) were defined as AEs that had onset on or after the day of first BRV dose in EP0085 study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 50 Percent (%) Responder Rate in Partial Seizure Frequency Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants | Baseline of EP0083 or N01358 and up to 84 months of Evaluation Period | The seizure frequency was calculated as number of seizures per 28 days. 50% responders were defined as a participant with a \>= 50% reduction in seizure frequency from the baseline period over the post-baseline period. Percentages are based on the number of participants who performed the seizure assessment at each time point. Evaluation Period values for seizure frequency were calculated from the seizure diary data collected during the Evaluation Period on/after the first BRV administration. |
| Percent Change in Partial Seizure Frequency Per 28 Days From Baseline of Directly Enrolled Study Participants to the Evaluation Period | Baseline (8 weeks prior to BRV administration), up to 39 months of Evaluation Period | The seizure frequency was calculated as number of seizures per 28 days. For direct enrollers, the Baseline Period was defined as seizure counts collected from 8 weeks prior to the first BRV administration in EP0085. Change in seizure frequency is calculated as the seizure frequency at the evaluation time point minus the seizure frequency at Baseline of directly enrolled participants. A negative value in percent change from Baseline indicates a decrease in PSF from Baseline. Evaluation Period values for seizure frequency were calculated from the seizure diary data collected during the Evaluation Period on/after the first BRV administration. |
| 50 % Responder Rate in Partial Seizure Frequency Per 28 Days Over the Evaluation Period for Directly Enrolled Study Participants | Baseline (8 weeks prior to BRV administration), up to 39 months of Evaluation Period | The seizure frequency for directly enrolled participants was calculated as number of seizures per 28 days from 8 weeks prior to BRV administration. 50% responders were defined as a participant with a \>= 50% reduction in seizure frequency from the Baseline Period over the post-baseline period. Percentages are based on the number of participants who performed the seizure assessment at each time point. For direct enrollers, the Baseline Period was defined as seizure counts collected from 8 weeks prior to the first BRV administration in EP0085. Evaluation Period values for seizure frequency were calculated from the seizure diary data collected during the Evaluation Period on/after the first BRV administration. |
| Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 6 Months During the Evaluation Period for Rollover Study Participants | During the Evaluation Period (up to 84 months) | A study participant was considered seizure free, if no seizure occurred during 6 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. |
| Percent Change in Partial Seizure Frequency (PSF) Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants | Baseline of EP0083 or N01358 and up to 84 months of Evaluation Period | The seizure frequency was calculated as number of seizures per 28 days. Percent change of 28 day PSF from Baseline was defined as the percentage reduction of 28 day PSF for a designated post-baseline period in EP0085 compared with the Baseline 28 day PSF in the core study. Change in seizure frequency from Baseline was calculated: percent change = (\[Baseline 28 day PSF - Post Baseline 28 day PSF\]/\[Baseline 28 day PSF\]) × 100. For rollovers, the Baseline period was obtained from the core studies of EP0083 and N01358 directly. A negative value in percent change from Baseline indicates a decrease in PSF from Baseline. Evaluation Period values for seizure frequency were calculated from the seizure diary data collected during the Evaluation Period on/after the first BRV administration. |
| Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Rollover Study Participants | During the Evaluation Period (up to 84 months) | A study participant was considered seizure free (partial, all epileptic seizure), if no seizure occurred during the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. |
| Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 6 Months During the Evaluation Period for Directly Enrolled Study Participants | During the Evaluation Period (up to 39 months) | A study participant was considered seizure free, if no seizure occurred during 6 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. |
| Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 12 Months During the Evaluation Period for Directly Enrolled Study Participants | During the Evaluation Period (up to 39 months) | A study participant was considered seizure free, if no seizure occurred during 12 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. |
| Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Directly Enrolled Study Participants | During the Evaluation Period (up to 39 months) | A study participant was considered seizure free (partial, all epileptic seizure), if no seizure occurred during the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. |
| Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 12 Months During the Evaluation Period for Rollover Study Participants | During the Evaluation Period (up to 84 months) | A study participant was considered seizure free, if no seizure occurred during 12 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period. |
Countries
China, Japan
Participant flow
Recruitment details
The study started to enroll participants in August 2017 and concluded in December 2024.
Pre-assignment details
The Participant Flow refers to the Safety Set (SS). Study consisted of the Evaluation period (duration for rollover participants - 84 Months and for direct enrollers - 39 Months); Down-titration period (4 weeks); drug-free period (2 weeks).
Participants by arm
| Arm | Count |
|---|---|
| EP0083 Placebo Participants who received Placebo in study EP0083 (NCT03083665) and completed the Treatment and Transition Period of study EP0083 are rolled over to this study and received brivaracetam (BRV) 50 milligram per day (mg/day) two times (bid) (in total 100 mg/day) at Visit 1 (study entry) and were maintained at this dose for at least 2 weeks unless the participant was unable to tolerate treatment during evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. up to 84 months). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants' s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study. | 54 |
| EP0083 BRV All Participants rolled over from study EP0083 received BRV 50 mg/day bid (in total 100 mg/day) at Visit 1 (study entry) and were maintained at this dose for at least 2 weeks unless the participant was unable to tolerate treatment during evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. up to 84 months). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants' s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study. | 112 |
| N01379 BRV Participants rolled over from study N01379 (NCT01339559) (core study N01358 \[NCT01261325\]) received BRV 200 mg/day during the evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. up to 84 months). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants' s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study. | 7 |
| Direct Enrollers BRV Participants directly enrolled in this study received BRV 50mg bid (in total 100 mg/day) at Visit 1 (study entry) and were maintained at this dose for at least 2 weeks unless the participant was unable to tolerate treatment during evaluation period (from Visit 1 to end of study visit or early discontinuation visit i.e. Up to 84 Month, however, were evaluated for 39 months only due to late enrollment). Upon completion or early discontinuation from EP0085, there was a Down-Titration Period of 4 weeks to decrease in dose in steps on a weekly basis, up to 25 mg/day, followed by a 2-week Study Drug-Free Period during which the participant did not receive study drug. The BRV dose was adjusted (based on the individual participants' s seizure control and tolerability) between 50 mg/day and 200 mg/day during the study. | 34 |
| Total | 207 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Admission To Geriatric Health Facility | 0 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 2 | 4 | 0 | 4 |
| Overall Study | Epilepsy Surgery | 0 | 1 | 2 | 0 |
| Overall Study | Investigator's Judgment | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 5 | 14 | 1 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Patient requested to change hospital | 0 | 0 | 0 | 1 |
| Overall Study | PI's opinion:Subject noncompliant with medication | 0 | 1 | 0 | 0 |
| Overall Study | Pregnancy Event | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 2 | 0 | 1 |
| Overall Study | Request From The Sponsor | 0 | 1 | 0 | 0 |
| Overall Study | She wanted to change other therapeutic medication | 1 | 0 | 0 | 0 |
| Overall Study | Subject did not follow procedure or study drug | 0 | 1 | 0 | 0 |
| Overall Study | Subject moved to kanagawa (faraway from clinic) | 0 | 1 | 0 | 0 |
| Overall Study | Subjects did not follow procedures or medication | 0 | 1 | 0 | 0 |
| Overall Study | Subjects felt no effect;want to discontinue study | 0 | 1 | 0 | 0 |
| Overall Study | Subject stopped drug; did not wish to continue | 0 | 1 | 0 | 0 |
| Overall Study | Subjects underweight; intolerant to study drugs | 0 | 1 | 0 | 0 |
| Overall Study | The Subject Go Abroad and Not Return | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 7 | 0 | 4 |
Baseline characteristics
| Characteristic | EP0083 Placebo | EP0083 BRV All | N01379 BRV | Direct Enrollers BRV | Total |
|---|---|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 11.6 | 35.8 years STANDARD_DEVIATION 13.5 | 40.7 years STANDARD_DEVIATION 10.9 | 42.2 years STANDARD_DEVIATION 18.6 | 36.7 years STANDARD_DEVIATION 14.1 |
| Age, Customized 12 - <18 yrs | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 7 Participants |
| Age, Customized 18 - <65 yrs | 52 Participants | 104 Participants | 7 Participants | 29 Participants | 192 Participants |
| Age, Customized 65 - <85 yrs | 0 Participants | 4 Participants | 0 Participants | 3 Participants | 7 Participants |
| Age, Customized >=85 yrs | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 54 Participants | 112 Participants | 7 Participants | 34 Participants | 207 Participants |
| Race/Ethnicity, Customized Chinese | 22 Participants | 53 Participants | 0 Participants | 0 Participants | 75 Participants |
| Race/Ethnicity, Customized Japanese | 32 Participants | 58 Participants | 7 Participants | 34 Participants | 131 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 32 Participants | 53 Participants | 3 Participants | 19 Participants | 107 Participants |
| Sex: Female, Male Male | 22 Participants | 59 Participants | 4 Participants | 15 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 112 | 0 / 7 | 0 / 34 |
| other Total, other adverse events | 41 / 54 | 87 / 112 | 6 / 7 | 27 / 34 |
| serious Total, serious adverse events | 6 / 54 | 23 / 112 | 5 / 7 | 6 / 34 |
Outcome results
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent AEs (TEAEs) were defined as AEs that had onset on or after the day of first BRV dose in EP0085 study.
Time frame: From Baseline until end of the safety follow up (up to 88.5 months)
Population: The Safety Set consisted of all participants who took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EP0083 Placebo | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 88.9 percentage of participants |
| EP0083 BRV All | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 95.5 percentage of participants |
| N01379 BRV | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 100 percentage of participants |
| Direct Enrollers BRV | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 94.1 percentage of participants |
Secondary
50 Percent (%) Responder Rate in Partial Seizure Frequency Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants
The seizure frequency was calculated as number of seizures per 28 days. 50% responders were defined as a participant with a \>= 50% reduction in seizure frequency from the baseline period over the post-baseline period. Percentages are based on the number of participants who performed the seizure assessment at each time point. Evaluation Period values for seizure frequency were calculated from the seizure diary data collected during the Evaluation Period on/after the first BRV administration.
Time frame: Baseline of EP0083 or N01358 and up to 84 months of Evaluation Period
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EP0083 Placebo | 50 Percent (%) Responder Rate in Partial Seizure Frequency Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants | 66.7 percentage of responders |
| EP0083 BRV All | 50 Percent (%) Responder Rate in Partial Seizure Frequency Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants | 47.3 percentage of responders |
| N01379 BRV | 50 Percent (%) Responder Rate in Partial Seizure Frequency Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants | 57.1 percentage of responders |
Secondary
50 % Responder Rate in Partial Seizure Frequency Per 28 Days Over the Evaluation Period for Directly Enrolled Study Participants
The seizure frequency for directly enrolled participants was calculated as number of seizures per 28 days from 8 weeks prior to BRV administration. 50% responders were defined as a participant with a \>= 50% reduction in seizure frequency from the Baseline Period over the post-baseline period. Percentages are based on the number of participants who performed the seizure assessment at each time point. For direct enrollers, the Baseline Period was defined as seizure counts collected from 8 weeks prior to the first BRV administration in EP0085. Evaluation Period values for seizure frequency were calculated from the seizure diary data collected during the Evaluation Period on/after the first BRV administration.
Time frame: Baseline (8 weeks prior to BRV administration), up to 39 months of Evaluation Period
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EP0083 Placebo | 50 % Responder Rate in Partial Seizure Frequency Per 28 Days Over the Evaluation Period for Directly Enrolled Study Participants | 26.5 percentage of responders |
Secondary
Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Directly Enrolled Study Participants
A study participant was considered seizure free (partial, all epileptic seizure), if no seizure occurred during the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period.
Time frame: During the Evaluation Period (up to 39 months)
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EP0083 Placebo | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Directly Enrolled Study Participants | Participants with partial seizure-freedom | 5.9 percentage of participants |
| EP0083 Placebo | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Directly Enrolled Study Participants | Participants with all-type seizure-freedom | 5.9 percentage of participants |
Secondary
Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Rollover Study Participants
A study participant was considered seizure free (partial, all epileptic seizure), if no seizure occurred during the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period.
Time frame: During the Evaluation Period (up to 84 months)
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EP0083 Placebo | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Rollover Study Participants | Participants with partial seizure-freedom | 1.9 percentage of participants |
| EP0083 Placebo | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Rollover Study Participants | Participants with all-type seizure-freedom | 1.9 percentage of participants |
| EP0083 BRV All | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Rollover Study Participants | Participants with partial seizure-freedom | 7.1 percentage of participants |
| EP0083 BRV All | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Rollover Study Participants | Participants with all-type seizure-freedom | 7.1 percentage of participants |
| N01379 BRV | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Rollover Study Participants | Participants with partial seizure-freedom | 14.3 percentage of participants |
| N01379 BRV | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types During the Evaluation Period for Rollover Study Participants | Participants with all-type seizure-freedom | 14.3 percentage of participants |
Secondary
Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 12 Months During the Evaluation Period for Directly Enrolled Study Participants
A study participant was considered seizure free, if no seizure occurred during 12 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period.
Time frame: During the Evaluation Period (up to 39 months)
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EP0083 Placebo | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 12 Months During the Evaluation Period for Directly Enrolled Study Participants | 15.4 percentage of participants |
Secondary
Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 12 Months During the Evaluation Period for Rollover Study Participants
A study participant was considered seizure free, if no seizure occurred during 12 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period.
Time frame: During the Evaluation Period (up to 84 months)
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EP0083 Placebo | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 12 Months During the Evaluation Period for Rollover Study Participants | 8.3 percentage of participants |
| EP0083 BRV All | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 12 Months During the Evaluation Period for Rollover Study Participants | 14.0 percentage of participants |
| N01379 BRV | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 12 Months During the Evaluation Period for Rollover Study Participants | 33.3 percentage of participants |
Secondary
Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 6 Months During the Evaluation Period for Directly Enrolled Study Participants
A study participant was considered seizure free, if no seizure occurred during 6 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period.
Time frame: During the Evaluation Period (up to 39 months)
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EP0083 Placebo | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 6 Months During the Evaluation Period for Directly Enrolled Study Participants | 24.1 percentage of participants |
Secondary
Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 6 Months During the Evaluation Period for Rollover Study Participants
A study participant was considered seizure free, if no seizure occurred during 6 consecutive months in the Evaluation Period and if met all of the following criteria: - the participant completed the designated period during the Evaluation Period - the participant has at least 90% non-missing diary days during the period of time - the participant did not report any seizures during the period.
Time frame: During the Evaluation Period (up to 84 months)
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EP0083 Placebo | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 6 Months During the Evaluation Period for Rollover Study Participants | 15.4 percentage of participants |
| EP0083 BRV All | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 6 Months During the Evaluation Period for Rollover Study Participants | 19.8 percentage of participants |
| N01379 BRV | Percentage of Participants Continuously Seizure-free for Partial Seizure and All Seizure Types (Partial, Generalized, and Unclassified Epileptic Seizure) for at Least 6 Months During the Evaluation Period for Rollover Study Participants | 28.6 percentage of participants |
Secondary
Percent Change in Partial Seizure Frequency Per 28 Days From Baseline of Directly Enrolled Study Participants to the Evaluation Period
The seizure frequency was calculated as number of seizures per 28 days. For direct enrollers, the Baseline Period was defined as seizure counts collected from 8 weeks prior to the first BRV administration in EP0085. Change in seizure frequency is calculated as the seizure frequency at the evaluation time point minus the seizure frequency at Baseline of directly enrolled participants. A negative value in percent change from Baseline indicates a decrease in PSF from Baseline. Evaluation Period values for seizure frequency were calculated from the seizure diary data collected during the Evaluation Period on/after the first BRV administration.
Time frame: Baseline (8 weeks prior to BRV administration), up to 39 months of Evaluation Period
Population: The FAS consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on DRC during the Evaluation Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EP0083 Placebo | Percent Change in Partial Seizure Frequency Per 28 Days From Baseline of Directly Enrolled Study Participants to the Evaluation Period | -32.6 percent change |
Secondary
Percent Change in Partial Seizure Frequency (PSF) Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants
The seizure frequency was calculated as number of seizures per 28 days. Percent change of 28 day PSF from Baseline was defined as the percentage reduction of 28 day PSF for a designated post-baseline period in EP0085 compared with the Baseline 28 day PSF in the core study. Change in seizure frequency from Baseline was calculated: percent change = (\[Baseline 28 day PSF - Post Baseline 28 day PSF\]/\[Baseline 28 day PSF\]) × 100. For rollovers, the Baseline period was obtained from the core studies of EP0083 and N01358 directly. A negative value in percent change from Baseline indicates a decrease in PSF from Baseline. Evaluation Period values for seizure frequency were calculated from the seizure diary data collected during the Evaluation Period on/after the first BRV administration.
Time frame: Baseline of EP0083 or N01358 and up to 84 months of Evaluation Period
Population: The Full Analysis Set (FAS) consisted of all participants who took at least 1 dose of study medication and have at least 1 seizure record on Daily Record Card (DRC) during the Evaluation Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EP0083 Placebo | Percent Change in Partial Seizure Frequency (PSF) Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants | 60.6 percent change |
| EP0083 BRV All | Percent Change in Partial Seizure Frequency (PSF) Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants | 43.2 percent change |
| N01379 BRV | Percent Change in Partial Seizure Frequency (PSF) Per 28 Days From Baseline of EP0083 or N01358 to the Evaluation Period for Rollover Study Participants | 67.0 percent change |