STUDY OF ADJUNCTIVE ADMINISTRATION OF BRIVARACETAM INSUBJECTS FROM =1 MONTH TO <16 YEARS OLD WITH EPILEPSY

Conditions: ocalization-related, generalized or undetermined whether focal or generalized epileptic syndrome, according to ILAE classification
MedDRA version: 14.0Level: PTClassification code 10015037Term: EpilepsySystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2006-006536-22-CZ

Lead Sponsor: CB Pharma SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 100

Inclusion Criteria

1. 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). In addition, a Consent form or a specific Assent form, where required, will be signed and dated by minors.
2. Subject/parent(s)/legal representative(s) is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule or medication intake according to the judgment of the Investigator.
3. Localization-related, generalized or undetermined whether focal or generalized epileptic syndrome, according to ILAE classification.
4. Presence of an EEG compatible with the clinical diagnosis of epilepsy.
5. Subject having at least 1 seizure (any type) during the 3 weeks before V1.
6. Subject taking at least 1 but no more than 3 concomitant AEDs. All AEDs need to be at a stable dose for at least 7 days prior to V1 and no additions or deletions of AEDs will be permitted. The dose of any concomitant AED will have to remain stable from V1 through the collection of PK samples. Vagal nerve stimulator stable for at least 2 weeks before V1, is allowed and will be counted as a concomitant AED. Benzodiazepine taken more than once a week (for any indication) will be considered as a concomitant AED.
7. The subject is male or female and is between =1 month and <16 years of age at V1.
8. Body weight at V1 is at least 3kg for infants.
9. Female subjects without childbearing potential (premenarcheal or surgically sterile) are eligible.
10. Female subjects with childbearing potential who are not sexually active are eligible. Subjects need to notify the Investigator if there is an anticipated change in their status.
11. Adolescent female subjects with childbearing potential who are sexually active are eligible if they use a medically accepted contraceptive method. Oral or depot contraceptive treatment with at least ethinylestradiol 30µg per intake (or ethinylestradiol 50µg per intake if associated with any strong inducer [eg, carbamazepine, phenobarbital, primidone, phenytoin, oxcarbazepine, St. John’s Wort, rifampicin]),
monogamous relationship with vasectomized partner, or double-barrier contraception are acceptable methods. The subject must understand the consequences and potential risks of inadequately protected sexual activity, be educated about and understand the proper use of contraceptive methods, and undertake to inform the Investigator of any potential change in status.
12. Females with childbearing potential must have a negative pregnancy test at V1.
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pregnant or nursing females.
2. Concomitant use of LEV at V1. In addition, the use of LEV is prohibited for at least 4 weeks prior to V1.
3. 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.
4. History of status epilepticus in the last month prior to V1 or during study Baseline.
5. History or presence of pseudoseizures.
6. Subject suffering only from febrile seizures.
7. Subject 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 V1.
8. Subjects treated with vigabatrin who have visual field defects.
9. Subject has an allergy to pyrrolidone derivatives, investigational product excipients or a history of multiple drug allergies.
10. 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).
11. Subject has an underlying disease or is receiving a treatment that may interfere with the absorption, distribution, metabolism, and elimination of the study drug.
12. Subject has any medical condition that might interfere with his/her study participation, ie, serious infection, scheduled elective surgery, etc.
13. Subject has a history of suicide attempt or current suicidal ideation and/or behavior.
14. Terminal illness.
15. Subject has any clinically significant deviations from reference range values for laboratory parameters as determined by the Investigator.
16. Clinically relevant ECG abnormality according to Investigator.
17. Subject had major surgery within 6 months prior to V1.
18. Subject received any investigational drug or device within the 30 days prior to V1. The use of AEDs marketed for adults but not approved for pediatric use is not considered to be investigational” for the purposes of this study.
19. Investigators and co-Investigators’ children may not be included as subjects in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To characterize the steady-state PK of BRV and its metabolites in subjects from =1 month to<br><16 years of age, evaluate their relationship with physiological developmental variables, and<br>develop dosing adaptations.;Secondary Objective: • To document the short-term safety and tolerability of BRV<br>• To gain preliminary information on the efficacy of BRV in children with various<br>epileptic syndromes<br>• To assess compliance to study drug oral solution;Primary end point(s): The primary variables are the plasma concentrations of BRV and its metabolites ucb 42145 (acid), ucb 100406-1 (hydroxy), and ucb 107092-1 (hydroxyacid), and plasma concentrations of concomitant AEDs;Timepoint(s) of evaluation of this end point: Day 7 (v3), Day 14 (v4), Day 21 (V5)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): SAFETY<br>• Adverse events<br>• Safety laboratory tests (hematology, biochemistry, endocrinology, and urinalysis for subjects =4 years old)<br>• ECGs<br>• Vital signs (blood pressure, pulse rate, and body temperature)<br>• Physical (Tanner scale) and neurological examination<br>• Psychiatric and mental status<br>• Body weight and height<br>• Achenbach CBCL at Baseline for children 18 months and older (CBCL/1½-5 and CBCL/6-18) assessing behavior;Timepoint(s) of evaluation of this end point: Some or all of the secondary endopoints are evaluated on: Day -7 (v1), Day 1 (v2), Day 7 (v3), Day 14 (v4), Day 21 (v5), Day 35 (v6), Day 49 (v7)

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