Open-label Long-term Study of Adjunctive Brivaracetam in Pediatric Subjects With Epilepsy

Exclusion Criteria

• •All Subjects:
• •Subject is a pregnant or nursing female
• •Subject has severe medical, neurological, or psychiatric disorders or laboratory values, which may have an impact on the safety of the subject.
• •Subject has planned participation in any clinical study of another investigational drug or device.
• •Subject has \>1.5x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or \>1.0xULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are \>ULN and \<1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin \<35%). N01349 subjects with a total bilirubin \> ULN may be considered for the study if benign unconjugated hyperbilirubinemia is suspected in the context of prolonged neonatal jaundice, after discussion with the medical monitor. For randomized subjects with a baseline result \>ULN for ALT, AST, ALP, or total bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the eCRF. If subject has \>ULN ALT, AST, or ALP that does not meet the exclusion limit at the baseline referenced in Table 5-1 for LTFU subjects and at the Screening Visit for directly enrolled subjects, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the subject must be discussed with the Medical Monitor. Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated once for confirmation. This includes re-screening.
• •Subject has chronic liver disease.
• •Long Term Follow-up Subjects:
• •Subject had hypersensitivity to BRV or excipients or comparative drugs as stated in this protocol during the course of the core study.
• •Subject had poor compliance with the visit schedule or medication intake in the core study.
• •Subject ≥6 years of age has a lifetime history of suicide attempt (including actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at the EV. If a subject has active suicidal ideation without a specific plan as indicated by a positive response ("Yes") to Question 4 of Columbia-Suicide Severity Rating Scale (C SSRS) at the EV, the subject should be referred immediately to a Mental Healthcare Professional and may be excluded from the study based upon the Investigator's judgment of benefit/risk of continuing the subject in the study/on study medication.
• •Directly Enrolled Subjects:
• •Subject has previously received BRV.
• •Subject had concomitant use of LEV at the ScrV. In addition, the use of LEV is prohibited for at least 4 weeks prior to the ScrV.
• •Subject has epilepsy secondary to a progressive cerebral disease or tumor, or any other progressively neurodegenerative disease. Stable arteriovenous malformations, meningiomas or other benign tumors may be acceptable according to Investigator's opinion.
• •Subject has a history of primary generalized epilepsy.
• •Subject has a history of status epilepticus in the month immediately prior to the ScrV or during the Up Titration Period.
• •Subject has a history or presence of pseudoseizures.
• •Subject is suffering only from febrile seizures.
• •Subject is on felbamate with less than 18 months continuous exposure. Subject who has taken felbamate for a combined duration of treatment and wash out of \<18 months before the ScrV.
• •Subjects treated with vigabatrin who have visual field defects.
• •Subject has an allergy to pyrrolidone derivatives or investigational product excipients or a history of multiple drug allergies.
• •Subject has any clinically significant acute or chronic illness as determined during the physical examination or from other information available to the Investigator (eg, bone marrow depression, chronic hepatic disease, severe renal impairment, psychiatric disorder).
• •Subject has an underlying disease or is receiving a treatment that may interfere with the absorption, distribution, metabolism, and elimination of the study drug.
• •Subject has any medical condition that might interfere with his/her study participation (eg, serious infection or scheduled elective surgery).
• •Subject has a terminal illness.
• •Subject has any clinically significant deviations from reference range values for laboratory parameters as determined by the Investigator.
• •Subject has a clinically relevant ECG abnormality according to the Investigator.
• •Subject had major surgery within 6 months prior to the ScrV.
• •Subject received any investigational drug or device within the 30 days prior to the ScrV.