OPEN-LABEL, SINGLE-ARM, MULTICENTER, LONG-TERM STUDY TO EVALUATE SAFETY AND EFFICACY OF BRIVARACETAM USED AS ADJUNCTIVE TREATMENT IN PEDIATRIC SUBJECTS WITH EPILEPSY;P/297/2019 (POS indication)
- Conditions
- epilepsyseizures10039911
- Registration Number
- NL-OMON50183
- Lead Sponsor
- CB Pharma
- Brief Summary
Trial never started
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 4
To be eligible to participate in this study, all of the following criteria must
be met as specified. , # Inclusion criteria for all subjects, - An
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved
written Informed Consent form is signed and dated by the parent(s) or legal
representative(s). The Consent form or a specific Assent form, where required,
will be signed and dated by minors., - Subject/legal representative is
considered reliable and capable of adhering to the protocol (eg, able to
understand and complete diaries), visit schedule, or medication intake
(including BRV oral solution or tablets) according to the judgment of the
Investigator., - For female subjects, the subject is, 1) Not of childbearing
potential OR Of childbearing potential, and
- Is not sexually active
- Has a negative pregnancy test, OR , 2) Of childbearing potential, and Is
sexually active, Has a 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. Medically acceptable contraceptive methods for
the study include, but are not limited to:, Oral or depot contraceptive
treatment with at least ethinylestradiol 30*g per intake or ethinylestradiol
50*g per intake if also taking one of the following: carbamazepine,
phenobarbital, primidone, phenytoin, oxcarbazepine, St. John's Wort, or
rifampicin, Barrier contraception: intrauterine device, diaphragm with
spermicide, male or female condom with spermicide, Abstinence from sexual
intercourse, # Inclusion criteria for LTFU subjects only, - Male or female
subjects having participated in a core study with BRV with a confirmed
diagnosis of epilepsy and for whom a reasonable benefit from long-term
administration of BRV is expected., # Inclusion criteria for directly enrolled
subjects only, - Subject is a male or female *4 years to <17 years of age.,
- Subject has a clinical diagnosis of POS according to the 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 AED
(concurrently or sequentially)., - Subject had at least 1 seizure (POS) during
the 3 weeks before the 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.
Subjects are not permitted to enroll in the study if any of the following
criteria are met as specified. , # Exclusion criteria for 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 any
medical condition, which in the Investigator*s opinion, warrants exclusion.,
-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)., -Subject has chronic liver disease., # Exclusion
criteria for LTFU subjects only, - 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., # Exclusion
criteria for directly enrolled subjects only, - 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 treatm
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Incidence of treatment-emergent adverse events (TEAEs) during the study.<br /><br>Incidence of treatment-emergent serious adverse events (SAEs) during the study</p><br>
- Secondary Outcome Measures
Name Time Method <p>For subjects *2 years of age (based on daily record card (DRC) data):<br /><br>1. Absolute change in 28-days adjusted partial-onset seizures (POS) frequency<br /><br>from Baseline to the end of the Evaluation Period in subjects with POS only<br /><br>2. Percent change in 28-days adjusted partial-onset seizures (POS) frequency<br /><br>from Baseline to the end of the Evaluation Period in subjects with POS only<br /><br>3. 50% responder rate for total seizures (all types)<br /><br>For subjects <2 years of age (based on EEG data [recorded at least 24 hours])<br /><br>or subjects with typical absence seizures (based on EEG data):<br /><br>4. Absolute change in average daily frequency of partial-onset-seizures (POS)<br /><br>in subjects with POS only<br /><br>5. Percent change in average daily frequency of partial-onset-seizures (POS) in<br /><br>subjects with POS only<br /><br>6. 50% responder rate for total seizures (all types)</p><br>