safety and tolerability of intravenous brivaracetam (infusion or bolus) as adjunctive antiepileptic therapy

Conditions: Epilepsy

Summary: this is a multicenter, open-label, 4-arm, randomized, parallel-group study to evaluate safety and tolerability of brivaracetam intravenous (brv iv) as adjunctive treatment for adults with epilepsy according to an initiation or a conversion scheme, during repeated dosing (100 mg/administration twice daily for 4.5 days).

eligible subjects will be randomized in a 1:1:1:1 ratio to the 4 treatment arms

Eligibility criteria:
inclusion criteria: * an institutional review board/independent ethics committee (irb/iec) approved written informed consent form signed and dated by the subject or by parent(s) or legal representative * subjects from 16 to 70 years * subjects with a body weight of \>/= 40 kg * female subjects without childbearing potential or female subjects with childbearing potential if they use a medically accepted contraceptive method * subject/legal representative considered as reliable and capable of adhering to the protocol * subjects with well-characterized focal or generalized epilepsy or epileptic syndrome * subjects with a history of partial-onset seizures whether or not secondarily generalized or primary generalized seizures * subjects being uncontrolled while treated with 1 to 2 permitted concomitant antiepileptic drugs (aeds) * permitted concomitant antiepileptic drugs (aeds) and vagus nerve stimulation (vns) being stable and at optimal dosage for the subject from at least 1 month before visit 1 and expected to be kept stable during the run-in and evaluation periods exclusion criteria: * mentally impaired subjects unable to understand the study purpose * history or presence of status epilepticus during 1 year preceding visit 1 or baseline * subjects on felbamate with less than 18 months continuous exposure before visit 1 * subjects currently on vigabatrin * subject taking any drug with possible relevant central nervous system effects except is stable from at least 1 month before visit 1 and expected to be kept stable during the trial * subjects taking any drug that may significantly influence the metabolism of brivaracetam (brv) except if the dose has been kept stable at least 1 month before visit 1, and is expected to be kept stable during the trial * history of cerebrovascular accident in the last 6 months * subjects suffering from severe cardiovascular disease or peripheral vascular disease * presence of any sign suggesting rapidly progressing brain disorder or brain tumor * any clinical conditions which impair reliable participation in the study or necessitate the use of medication not allowed by protocol * presence of a terminal illness * presence of a serious infection * subjects with a history of sever adverse hematologic reaction to any drug * subjects suffering from severe disturbance of hemostasis * impaired hepatic function: alanine aminotransferase (alt), aspartate aminotransferase (ast), gamma-glutamyltransferase (ggt) values of more than 3 times the upper limit of the reference range * subjects having clinically significant deviations from reference range values for laboratory parameters: creatinine clearance calculated \< 50 ml / min, platelets \< 100,000 / µl, or neutrophil cells \< 1,800 / µl * clinically significant electrocardiogram (ecg) abnormalities according to the investigator * history of suicide attempt * in the investigator's medical judgment, any current suicidal ideation or other serious psychiatric disorders requiring of having required hospitalization or medication * known allergic reaction or intolerance to pyrrolidone derivatives and / or investigational product excipients * known multiple drug allergies or severe drug allergy * pregnant or lactating women * known alcohol or drug addiction or abuse within the last 2 years * subject institutionalized under judicial decision * problems of venous accessibility * subject taking part in another clinical / pharmacological study in the month preceding enrollment (visit 1) * investigators, coinvestigators, their spouses or children, or any study collaborators * subjects previously treated with brivaracetam (brv) * subject previously screened within this study

Keywords: n01258 brivaracetam epilepsy iv intravenous