Epilepsy
Conditions
Keywords
Brivaracetam, Long-term Follow-up, Epilepsy, Partial Onset Seizures, Adjunctive treatment
Brief summary
N01372 study is to evaluate the long-term safety, tolerability, maintenance of efficacy of Brivaracetam (BRV); as well as the effect of BRV on subjects' health-related quality of life and to explore the direct medical resource use for BRV (for subjects entering N01372 from a study where pharmacoeconomic data was collected). BRV will be used at doses up to maximum of 200 mg/day, as adjunctive treatment in subjects aged 16 years or older with Epilepsy.
Detailed description
Flexible dosing up to 200 mg/day, twice daily (10, 25 and 50 mg oral film-coated tablets). The study will continue until either regulatory approval of BRV has been granted by any Health Authority in an indication of adjunctive treatment of Epilepsy, or until the Sponsor decides to close the study, or until the BRV development is stopped by the Sponsor.
Interventions
DRUGBrivaracetam
Flexible dosing, can up and down-titrate as needed.
Sponsors
UCB Pharma SA
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
* Subject is male or female and 16 years or older. Subjects under 18 years of age may be included only where legally permitted and ethically accepted * Subjects having completed the Treatment Period of an applicable previous BRV study, and have access to the present study * Subject for whom the investigator believes a reasonable benefit from the long-term administration of BRV may be expected * Female subjects without childbearing potential (postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method * Subjects must be able to take the oral film-coated tablets of BRV
Exclusion criteria
* Subject has developed hypersensitivity to any components of the Investigational Medicinal Product (IMP) or comparative drugs as stated in the protocol during the course of the prior study * Severe medical, neurological, or psychiatric disorders, or laboratory values that may have an impact on the safety of the subject * Poor compliance with the visit schedule or medication intake in the previous BRV study * 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 * Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (Yes) to either question 4 or question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at the last visit of the previous study or at the Entry Visit of this study if not completed at the last visit of the previous study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events (TEAEs) During Evaluation Period | From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months) | TEAEs were defined as AEs that had onset on or after the day of first study medication dose. An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Results are presented as the percentage of subjects with at least one treatment-emergent adverse event during this study. |
| Percentage of Subjects Withdrawn Due to an Adverse Event (AE) During the Evaluation Period | From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months) | An AE was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. Results are presented as the percentage of subjects withdrawn due to an AE. |
| Occurrence of a Serious Adverse Event (SAE) During the Evaluation Period | From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months) | SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity or are a congenital anomaly/birth defects. Results are presented as the percentage of subjects with at least one SAE during this study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Partial-Onset Seizure (POS) Type I Per 28 Days During the Evaluation Period for Subjects With Focal-onset Epilepsy | From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months) | The POS frequency is standardized to a 28-day duration. Results are presented as the median number of seizures per 28 days. |
| Percentage of Change in Partial-Onset-Seizure (POS) Type I Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period for Subjects With Focal-onset Epilepsy Entering N01372 From a Study Where Baseline Seizure Data Was Collected | From Baseline of the previous study to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 49 months) | The POS frequency is standardized to a 28-day duration. Results are presented as the median percentage of reduction per 28 days. Negative values indicate improvement from Baseline. |
| 50 % Responder Rate in Partial-Onset-Seizure (POS) Type I Frequency From Baseline of the Previous Study to the Evaluation Period for Subjects With Focal-onset Epilepsy Entering N01372 From a Study Where Baseline Seizure Data Was Collected | From Baseline of the previous study to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 49 months) | The POS frequency is standardized to a 28-day duration. A responder is defined as a subject with a \>=50% reduction in seizure frequency from the Baseline Period of the previous study. Results are presented as the percentage of subjects with 50 % responder rate in POS Type I frequency. |
Countries
France, Germany, Spain, United States
Participant flow
Recruitment details
This study started to enroll subjects in October 2012 and concluded in August 2016.
Pre-assignment details
Participant Flow refers to the Safety Set (SS), which consisted of all subjects who took at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Brivaracetam Focal Epilepsy This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. | 19 |
| Brivaracetam Generalized Epilepsy This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. | 7 |
| Total Title | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non compliance | 1 | 0 |
| Overall Study | Patient moving | 1 | 0 |
| Overall Study | Subject choice | 2 | 3 |
Baseline characteristics
| Characteristic | Brivaracetam Focal Epilepsy | Brivaracetam Generalized Epilepsy | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 7 Participants | 26 Participants |
| Age, Continuous Arithmetic mean (standard deviation) | 38.6 years STANDARD_DEVIATION 10.9 | 30.7 years STANDARD_DEVIATION 13.2 | 36.5 years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 12 Participants | 2 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 19 | 5 / 7 |
| serious Total, serious adverse events | 5 / 19 | 2 / 7 |
Outcome results
Primary
Incidence of Treatment Emergent Adverse Events (TEAEs) During Evaluation Period
TEAEs were defined as AEs that had onset on or after the day of first study medication dose. An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Results are presented as the percentage of subjects with at least one treatment-emergent adverse event during this study.
Time frame: From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam Focal Epilepsy (SS) | Incidence of Treatment Emergent Adverse Events (TEAEs) During Evaluation Period | 78.9 percentage of subjects |
| Brivaracetam Generalized Epilepsy (SS) | Incidence of Treatment Emergent Adverse Events (TEAEs) During Evaluation Period | 71.4 percentage of subjects |
Primary
Occurrence of a Serious Adverse Event (SAE) During the Evaluation Period
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity or are a congenital anomaly/birth defects. Results are presented as the percentage of subjects with at least one SAE during this study.
Time frame: From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)
Population: The analysis was performed on the Safety Set (SS), which consisted of all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam Focal Epilepsy (SS) | Occurrence of a Serious Adverse Event (SAE) During the Evaluation Period | 26.3 percentage of subjects |
| Brivaracetam Generalized Epilepsy (SS) | Occurrence of a Serious Adverse Event (SAE) During the Evaluation Period | 28.6 percentage of subjects |
Primary
Percentage of Subjects Withdrawn Due to an Adverse Event (AE) During the Evaluation Period
An AE was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. Results are presented as the percentage of subjects withdrawn due to an AE.
Time frame: From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam Focal Epilepsy (SS) | Percentage of Subjects Withdrawn Due to an Adverse Event (AE) During the Evaluation Period | 0 percentage of subjects |
| Brivaracetam Generalized Epilepsy (SS) | Percentage of Subjects Withdrawn Due to an Adverse Event (AE) During the Evaluation Period | 14.3 percentage of subjects |
Secondary
50 % Responder Rate in Partial-Onset-Seizure (POS) Type I Frequency From Baseline of the Previous Study to the Evaluation Period for Subjects With Focal-onset Epilepsy Entering N01372 From a Study Where Baseline Seizure Data Was Collected
The POS frequency is standardized to a 28-day duration. A responder is defined as a subject with a \>=50% reduction in seizure frequency from the Baseline Period of the previous study. Results are presented as the percentage of subjects with 50 % responder rate in POS Type I frequency.
Time frame: From Baseline of the previous study to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 49 months)
Population: The analysis was performed on the Efficacy Analysis Set (EAS), which consisted of subjects who took at least one dose of study drug and had at least one seizure daily record card (DRC) day during the Evaluation Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam Focal Epilepsy (SS) | 50 % Responder Rate in Partial-Onset-Seizure (POS) Type I Frequency From Baseline of the Previous Study to the Evaluation Period for Subjects With Focal-onset Epilepsy Entering N01372 From a Study Where Baseline Seizure Data Was Collected | 54.5 percentage of subjects |
Secondary
Frequency of Partial-Onset Seizure (POS) Type I Per 28 Days During the Evaluation Period for Subjects With Focal-onset Epilepsy
The POS frequency is standardized to a 28-day duration. Results are presented as the median number of seizures per 28 days.
Time frame: From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)
Population: The analysis was performed on the Efficacy Analysis Set (EAS), which consisted of subjects who took at least one dose of study drug and had at least one seizure daily record card (DRC) day during the Evaluation Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brivaracetam Focal Epilepsy (SS) | Frequency of Partial-Onset Seizure (POS) Type I Per 28 Days During the Evaluation Period for Subjects With Focal-onset Epilepsy | 0.4 Seizures per 28 days |
Secondary
Percentage of Change in Partial-Onset-Seizure (POS) Type I Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period for Subjects With Focal-onset Epilepsy Entering N01372 From a Study Where Baseline Seizure Data Was Collected
The POS frequency is standardized to a 28-day duration. Results are presented as the median percentage of reduction per 28 days. Negative values indicate improvement from Baseline.
Time frame: From Baseline of the previous study to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 49 months)
Population: The analysis was performed on the Efficacy Analysis Set (EAS), which consisted of subjects who took at least one dose of study drug and had at least one seizure daily record card (DRC) day during the Evaluation Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brivaracetam Focal Epilepsy (SS) | Percentage of Change in Partial-Onset-Seizure (POS) Type I Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period for Subjects With Focal-onset Epilepsy Entering N01372 From a Study Where Baseline Seizure Data Was Collected | -56.3 percentage of change |