Evaluation of Long-term Safety, and Efficacy of Brivaracetam (BRV) Used as Adjunctive Treatment in Subjects With Epilepsy

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-label, Multicenter, Follow-up Study to Evaluate the Long-term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Subjects Aged 16 Years or Older With Epilepsy Phase 3b

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Brivaracetam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brivaracetam<br>At Entry Visit (EV), subjects will start on the individualized Brivaracetam (BRV) dose that they had reached at the completion of the previous study. Dose adjustments of the Investigational Medicinal Product (IMP) are allowed at any time based on the clinical judgment of the investigator. The BRV dose can be increased or decreased in increments of 50 mg/day based on the individual subject's seizure control and/or tolerability; however, the BRV dose should not exceed 200 mg/day during the study and must always be administered as a symmetrical morning and evening dose. Upon completion or early discontinuation from this study, there will be a Down-Titration Period in steps of 50 mg/day on a weekly basis until 20 mg/day for 1 week is reached, followed by a Post-Treatment Period (between 2 and 4 weeks) during which the subject will not receive study drug. No down-Titration Period will be applicable if subjects are continued on BRV after they complete this study. | Drug: Brivaracetam<br>* Flexible dosing, can up and down-titrate as needed.<br>* Other names: UCB34714;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months) | 
| 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. | From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months) | 
| 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. | From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months) | 
| 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. | From Baseline of the previous study to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 49 months) | 
| 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. | From Baseline of the previous study to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 49 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brivaracetam, Long-term Follow-up, Epilepsy, Partial Onset Seizures, Adjunctive treatment