Open-label Long-term Study of Adjunctive Brivaracetam in Pediatric Subjects With Epilepsy
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: Brivaracetam (BRV)
Intervention description: The max BRV dose will be 5.0 mg/kg/day, not to exceed a dose of 200 mg/day for subjects with body weight >40kg. Subjects may receive oral solution or oral tablets. The LTFU subjects will start dosing in N01266 on the individualized BRV dose they were receiving at the completion of the core study. Subjects must be able to tolerate the min BRV dose specified in the core study to be eligible for entry into the Evaluation Period of N01266. Dose can be adjusted as considered necessary by the Investigator and required by the subject's medical condition. All subjects who prematurely discontinue the study should complete an EDV and have their BRV dose down titrated by a maximum of half the dose every week for a maximum of 4 weeks until a dose of 1 mg/kg/day (50 mg/day for subjects with body weights >50kg) is reached.
Intervention MeSH terms: Brivaracetam
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 257.0
Sex: All
Minimum age: 28 Days
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Brivaracetam; Epilepsy; Child; Infant; Adolescents; Partial onset seizures

Summary:

      This study will evaluate the safety and tolerability of brivaracetam in pediatric subjects
      with epilepsy.
    

Eligibility criteria:

        Inclusion Criteria:

        All Subjects:

          -  Informed Consent form (ICF) is signed and dated by the parent(s) or legal
             representative(s)

          -  Subject/legal representative is considered reliable and capable of adhering to the
             protocol

          -  For female subjects:

          -  Subject is not of childbearing potential

        OR if women of childbearing potential, and sexually active only if:

          -  Adequate Contraceptive method

          -  Negative pregnancy test

          -  Understands the consequences and potential risks of inadequately protected sexual
             activity, understands and properly uses contraceptive methods, and is willing to
             inform the Investigator of any contraception changes

        Long Term Follow-up Subjects:

        - Male or female subjects having participated in a core study with a confirmed diagnosis of
        epilepsy and for whom a reasonable benefit from long-term administration of BRV is expected

        Directly Enrolled Subjects:

          -  Subject is a male or female ≥4 years to <17 years of age

          -  Subject has a clinical diagnosis of partial-onset seizures (POS) according to the
             International League Against Epilepsy (ILAE) classification

          -  Subject has an EEG compatible with the clinical diagnosis of POS

          -  Subject has been observed to have uncontrolled POS after an adequate course of
             treatment (in the opinion of the Investigator) with at least 1 antiepileptic drug
             (AED; concurrently or sequentially)

          -  Subject had at least 1 seizure (POS) during the 3 weeks before the Screening Visit
             (ScrV)

          -  Subject is taking at least 1 AED. All AEDs need to be at a stable dose for at least 7
             days before the ScrV. Vagal nerve stimulator stable for at least 2 weeks before the
             ScrV is allowed and will be counted as a concomitant AED. Benzodiazepines taken more
             than once a week (for any indication) will be considered as a concomitant AED

        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.