Protocol N01358 A Randomized, Double-Blind, Placebo Controlled, Multicenter, Parallel Group Study To Evaluate The Efficacy and Safety of Brivaracetam in Subjects (≥ 16 to 80 Years Old) with Partial Onset Seizures.
This adequate and well-controlled study will be performed to provide additional data confirming the efficacy and safety of BRV (brivaracetam) as an AED and to support a marketing authorization application/new drug application for BRV in the indication of adjunctive treatment in adults (≥16 years) with refractory Partial Onset Seizures whether or not secondarily generalized.
N01358 will assess BRV doses of 100 and 200mg/day. Consistent with the previous fixed dose Phase III studies , N01358 will include an 8-week Baseline Period and a 12-week Treatment Period.
The primary efficacy variable of N01358 will be Partial Onet Seizures (Type I) frequency per 28 days over the Treatment Period.
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved
written informed consent form is signed and dated by the subject or by the parent(s) or
2. 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
according to the judgment of the Investigator.
3. Subjects (male or female) from 16 to 80 years, both inclusive. Subjects under 18 years
may only be included where legally permitted and ethically accepted.
4. Subjects with a body weight ≥40kg.
5. Female subjects without childbearing potential (premenarcheal, postmenopausal for at
least 2 years, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method. Oral or depot contraceptive treatment with at least 30μg ethinylestradiol per intake [or 50μg ethinylestradiol 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. Well-characterized focal epilepsy/epileptic syndrome according to the 1989 International
League Against Epilepsy (ILAE) classification.
7. Presence of an EEG reading compatible with the clinical diagnosis of focal epilepsy
within the last 5 years.
8. Presence of a brain MRI/computed tomography (CT) scan performed within the last
9. Subjects having at least 8 Type I seizures [POS; focal seizures (according to the 1981
ILAE classification)] during the 8-week Baseline Period with at least 2 Type I seizures
during each 4-week interval of the Baseline Period.
10. Subjects having at least 2 partial onset seizures whether or not secondarily generalized
per month during the 3 months preceding V1.
11. Subjects being uncontrolled while treated by 1 or 2 permitted concomitant AED(s). Vagal
Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED.
12. Permitted concomitant AED(s) and VNS being stable and at optimal dosage for the
subject from at least 1 month (3 months for phenobarbital, phenytoin, and primidone)
before V1 and expected to be kept stable during the Baseline and Treatment Period.
Benzodiazepine taken more than once a week (for any indication) will be considered as a