Protocol N01379: 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.
This is a Phase III Long term Follow-Up Open label study to evaluate the safety and efficacy Brivaracetam in adult subjects with Partial Onset and Generalized Seizures.
The primary objective is to evaluate the long-term safety and tolerability of BRV at individualized doses up to a maximum of 200mg/day in epilepsy subjects.
* To evaluate the maintenance of efficacy of BRV over time
* To explore the effects of BRV on subjects[Right Quote] HRQoL
* To explore direct medical resource use
* To explore any change in socio-professional status
* To assess the role of gene variants of SV2 in affecting response to BRV (as part of a
DNA analysis at the program level)
The primary efficacy variable is the POS and Generalized seizure frequency standardized to a 28-day duration. This will be summarized by 3-month periods over the Evaluation Period.
Secondary efficacy variables are as follows:
1) Seizure frequency per 28 days for all seizure types (I+II+III) by 3-month periods over the Evaluation Period.
2) Proportion of seizure-free days for all seizure types (I+II+III) by 3-month periods over the Evaluation Period
3) Proportion of continuously seizure-free subjects for all seizure types (I+II+III) by 3-month periods over the Evaluation Period
4) Responder rate in POS and Generalized seizures by 3-month periods over the Evaluation Period. A responder is defined as a subject with a ≥50% reduction in seizure frequency from the Baseline Period for the double-blind study N01358.
5) addition of the Columbia Suicide Severity Rating Scale performed at every visit per FDA guidelines.
Subjects coming from N01358 study are offered to participate in Pharmacogenomic/DNA analysis. If the subject agrees and signs the Pharmacogenomic Consent the specimine will be collected at the Entry Visit. A blood sample Pharmacogenomic/DNA for analysis is obtained in order to explore a possible correlation between the SV2 gene variations and the subject[Right Quote]s response to BRV. Blood samples for DNA analysis will be collected only in adults where ethically accepted and authorized by legal authorities. The DNA analysis will be done in a separate report at the program level. Samples will be split into 2 aliquots and will be initially stored at the central laboratory and will then be shipped to the genotyping facility for DNA extraction and genotyping. Samples
will be stored at -20[Degrees]C for a period of up to 20 years.
This is a Phase 3, open-label, LTFU, multicenter, noncomparative, and single-arm study. The subject population will be adults (≥16 years) with refractory POS whether or not secondarily generalized. Subjects under 18 years may be included only where legally permitted and ethically accepted. Subjects must complete the Treatment Period of N01358 prior to enrollment into N01379. Upon completion or early discontinuation from N01379, there will be a Down-Titration Period, followed by a Posttreatment Period during which the subject will not receive study drug.
This LTFU study will run throughout the duration of the clinical development period of BRV, and will continue until a marketing authorization is granted by any Health Authority in an indication for the adjunctive treatment in adults (≥16 years) with refractory POS, whether or not secondarily generalized and generalized seizures, until the Sponsor decides to close the study,
1. An Independent Ethics Committee (IEC)/Institutional Review Board (IRB) approved written informed consent signed and dated by the subject or by parent(s) or legally acceptable representative. The consent form or a specific assent form, where required, will be signed and dated by minors. In countries and sites where a DNA analysis is accepted, an additional Informed Consent form will have to be signed by subjects coming from N01358. Deoxyribonucleic acid analysis will be performed only in adults, and the subject can withdraw consent to the use of the sample at any time. Mentally impaired subjects will be excluded. In case the consent is withdrawn, the site must request the destruction of the sample.
2. Male/female subject from 16 years or older. Subject under 18 years may only be included where legally permitted and ethically accepted. This site will only enroll subjects 18 years of age or older.
3. Subject completed the Treatment Period of N01358 or the Evaluation Period of N01258.
4. Subject for whom the Investigator believes a reasonable benefit from the long-term administration of BRV may be expected.
5. Female subject without childbearing potential (premenarcheal, postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subject with childbearing potential 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 enzyme 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.Abstinence will be considered as an acceptable method of contraception if the Investigator can document that the subject agrees to be compliant.
6. Subject/legally acceptable representative considered as reliable and capable of adhering to the protocol (eg, able to understand and complete diaries and questionnaires), visit schedule, or medication intake according to the judgment of the Investigator.