Efficacy Evaluation of Intravenous Brivaracetam and Phenytoin in Subjects With Nonconvulsive Electrographic Seizures

NCT ID: NCT02088957

Last Updated: 2018-07-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2014-10-31

Brief Summary

The primary objective of this study is to compare the efficacy of Brivaracetam and Phenytoin, both administered intravenously, in adult subjects experiencing nonconvulsive electrographic seizures.

Conditions

Nonconvulsive Electrographic Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Brivaracetam

Subjects will receive an acute intravenous (iv) dose of Brivaracetam (BRV) 200 mg as a bolus on Day 1. If seizures recur, a second iv bolus of BRV 100 mg can be given no sooner than 15 minutes after the first bolus. If the second acute bolus is not needed within12 hours after first iv bolus, BRV will be continued as 100 mg iv dose every 12 hours (bid). The total dose for the first 24 hours of treatment should not exceed a maximum dose of 400 mg. The rate of bolus administration is 50 mg (5 mL) undiluted BRV/min. On study Day 5 (or earlier), subjects will transition from iv to oral formulation, at comparable dosing for a maximum of 6 months.

Subjects should transition to oral medication as soon as they are able to swallow tablets.

Group Type: EXPERIMENTAL

Brivaracetam intravenous solution

Intervention Type: DRUG

• Active Substance: Brivaracetam
• Pharmaceutical Form: Solution for infusion
• Concentration: 10 mg/mL
• Route of Administration: Intravenous bolus use

Brivaracetam oral tablets

Intervention Type: DRUG

• Active Substance: Brivaracetam
• Pharmaceutical Form: Film-coated tablet
• Concentration: 10 mg and 25 mg tablets; Daily Dose: 200 mg/day (100 mg bid)
• Route of Administration: Oral use

Phenytoin

Subjects will receive an acute intravenous (iv) dose of Phenytoin (PHT) 20 mg/kg at a rate of 50 mg/min on Day 1. If seizures recur, a second acute dose of PHT iv will be given no sooner than 15 minutes after the first dose. Treatment with PHT iv will be continued with at least 2 daily divided doses according to site practice. Daily PHT dose can be adapted according to investigator's clinical judgment. On study Day 5 (or earlier), subjects will transition from iv to oral formulation at comparable dosing for a maximum of 6 months.

Subjects should transition to oral medication as soon as they are able to swallow tablets.

Group Type: ACTIVE_COMPARATOR

Phenytoin intravenous solution

Intervention Type: DRUG

• Active Substance: Phenytoin
• Pharmaceutical Form: Solution for infusion
• Concentration: 50 mg/mL
• Route of Administration: Intravenous use

Phenytoin oral tablets

Intervention Type: DRUG

• Active Substance: Phenytoin
• Pharmaceutical Form: Tablet
• Concentration: Weight based
• Route of Administration: Oral use

Interventions

Brivaracetam intravenous solution

• Active Substance: Brivaracetam
• Pharmaceutical Form: Solution for infusion
• Concentration: 10 mg/mL
• Route of Administration: Intravenous bolus use

Intervention Type: DRUG

Brivaracetam oral tablets

• Active Substance: Brivaracetam
• Pharmaceutical Form: Film-coated tablet
• Concentration: 10 mg and 25 mg tablets; Daily Dose: 200 mg/day (100 mg bid)
• Route of Administration: Oral use

Intervention Type: DRUG

Phenytoin intravenous solution

• Active Substance: Phenytoin
• Pharmaceutical Form: Solution for infusion
• Concentration: 50 mg/mL
• Route of Administration: Intravenous use

Intervention Type: DRUG

Phenytoin oral tablets

• Active Substance: Phenytoin
• Pharmaceutical Form: Tablet
• Concentration: Weight based
• Route of Administration: Oral use

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects ≥16 years. Subjects under 18 years may only be included where legally permitted and ethically accepted
• Subjects in the neurological intensive care unit (NICU) (or equivalent closely monitored environment) having brain insult including traumatic brain injury and having nonconvulsive electrographic seizures (NCES) confirmed by electroencephalogram (EEG), lasting a minimum of 10 seconds but not >30 minutes (minimum of 1 seizure in the last 6 hours) and treatment with an antiepileptic drug (AED) is required according to the physician's clinical judgment
• Subject is expected to be under cEEG monitoring with video surveillance in the Neuro ICU for at least 36 hours from the first administration of study drug

Exclusion Criteria

• Subject has history of severe adverse hematologic or cutaneous reaction to any drug
• Subject presenting with status epilepticus or nonconvulsive status epilepticus (NCSE) (ie, 1 continuous, convulsive or nonconvulsive, unremitting seizure lasting >30 minutes during Visit 1)
• Subject has been diagnosed with anoxic brain injury
• Subject has a known history of status epilepticus during the 6 months preceding Visit 1
• Subject is currently treated with Levetiracetam (LEV) or Phenytoin (PHT) or has been treated within the last 30 days before Visit 1 with LEV or PHT
• Subject is on felbamate with <18 months' exposure before Visit 1
• Subject has presence of any sign (clinical or imaging techniques) suggesting a rapidly progressing process such that the subject is not expected to survive >48 hours
• Subject has any clinical condition that would impair reliable participation in the study or necessitate the use of medications not allowed by the protocol

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

UCB BIOSCIENCES, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

UCB Clinical Trial Call Center

Role: STUDY_DIRECTOR

+1 877 822 9493 (UCB)

Locations

3

Lexington, Kentucky, United States

1

Jackson, Mississippi, United States

Countries

United States

Related Links

http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

N01394

Identifier Type: -

Identifier Source: org_study_id