Safety and Tolerability of Intravenous Brivaracetam (Infusion or Bolus) as Adjunctive Antiepileptic Therapy
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: Brivaracetam tablets; Brivaracetam bolus; Brivaracetam infusion; Placebo
Intervention description: 100 mg, intake twice daily (BID) for 7 days during Run-In Period; 10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period; 10 mL (= 100 mg) of Brivaracetam diluted in 90 mL 0.9 % isotonic saline sterile solution for intravenous administration infused over 15 minutes twice daily (BID) during Evaluation Period; 100 mg twice daily (BID) for 7 days during Run-In Period
Intervention MeSH terms: Brivaracetam
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 105.0
Sex: All
Minimum age: 16 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: N01258; Brivaracetam; Epilepsy; IV; intravenous

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).
    

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