Safety and Tolerability of Intravenous Brivaracetam (Infusion or Bolus) as Adjunctive Antiepileptic Therapy

UCB

Status and phase: Completed; Phase 3

Conditions: Epilepsy

Treatments: Drug: Brivaracetam bolus; Other: Placebo; Drug: Brivaracetam infusion; Drug: Brivaracetam tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT01405508

2008-004714-27 (EudraCT Number)

N01258

Details and patient eligibility

About

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).

Full description

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

Enrollment: 105 patients

Sex: All

Ages: 16 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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105 participants in 4 patient groups

Placebo tablets / Brivaracetam bolus

Experimental group

Description:

Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days. Down-Titration: * If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In * If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week

Treatment:

Drug: Brivaracetam bolus

Other: Placebo

Brivaracetam (BRV) tablets / BRV bolus

Experimental group

Description:

Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days. Down-Titration: * If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In * If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week

Treatment:

Drug: Brivaracetam tablets

Drug: Brivaracetam bolus

Placebo tablets / Brivaracetam infusion

Experimental group

Description:

Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days. Down-Titration: * If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In * If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week

Treatment:

Other: Placebo

Drug: Brivaracetam infusion

Brivaracetam (BRV) tablets / BRV infusion

Experimental group

Description:

Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days. Down-Titration: * If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In * If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week

Treatment:

Drug: Brivaracetam tablets

Drug: Brivaracetam infusion