A Dose-ranging Study With Brivaracetam in Patients From 16 to 65 Years With Refractory Partial Onset Seizures.

A Multicenter, Double-blind, Randomized, Placebo-controlled, 4 Parallel Groups, Dose-ranging Trial Evaluating the Efficacy and Safety of Brivaracetam Used as Adjunctive Treatment at Doses of 5, 20 and 50 mg/Day in b.i.d. Administration (Oral Tablets of 2.5 or 10 mg) for a Maximum of 7 Weeks in Subjects From 16 to 65 Years With Refractory Epilepsy Suffering From Partial Onset Seizures Whether or Not Secondarily Generalized

This trial will evaluate the efficacy and safety of brivaracetam (at doses of 5, 20 and 50 mg/day in twice a day administration) as add-on therapy in subjects with focal epilepsy.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Other: Placebo; Drug: Brivaracetam

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Florianopolis, Brazil
  • Salvador, Brazil
  • Sao Paulo, Brazil
• India
  • Bangalore, India
  • Hyderabad, India
  • Lucknow, India
  • Parel Mumbai, India
  • Trivandrum, India
• Mexico
  • Aguascalientes, Mexico
  • Chichuahua, Mexico
  • Chihuahua, Mexico
  • Guadalajara, Mexico
  • Monterrey, Mexico
  • San Luis Potosi, Mexico
  • Valle Oriente Garza Garcia, Mexico
  • Zapopan, Mexico
• United States
  • Arizona
    • Phoenix, Arizona, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Fresno, California, United States
  • Florida
    • Bradenton, Florida, United States
    • Jacksonville, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
  • Kentucky
    • Paducah, Kentucky, United States
  • Louisiana
    • Ruston, Louisiana, United States
  • Maryland
    • Bethesda, Maryland, United States
  • Massachusetts
    • Burlington, Massachusetts, United States
  • Michigan
    • Grand Rapids, Michigan, United States
  • Minnesota
    • Rochester, Minnesota, United States
  • Mississippi
    • Tupelo, Mississippi, United States
  • Missouri
    • Chesterfield, Missouri, United States
  • Montana
    • Great Falls, Montana, United States
  • New Jersey
    • Englewood Cliffs, New Jersey, United States
    • Toms River, New Jersey, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Wilmington, North Carolina, United States
  • Ohio
    • Columbus, Ohio, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
  • Rhode Island
    • Woonsocket, Rhode Island, United States
  • South Carolina
    • Greenville, South Carolina, United States
  • Texas
    • Dallas, Texas, United States
    • Houston, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male/female from 16 to 65 years
• Well-characterized focal epilepsy or epileptic syndrome according to the International League Against Epilepsy (ILAE) classification
• History of partial onset seizures
• Subjects having at least 4 partial onset seizures during the 4-week Baseline Period and at least 2 partial onset seizures during the 3 months prior to Visit 1
• Subjects taking 1 or 2 concomitant Antiepileptic drugs (AED(s)) that have been at a stable dose.

Exclusion Criteria:

• Seizure type IA non-motor as only seizure type
• Seizures occurring only in clusters
• Status epilepticus during the last 2 years before Visit 1
• History of cerebrovascular accident (CVA)
• Presence of any sign suggesting rapidly progressing brain disorder or brain tumor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching Placebo tablets administered twice a day	Other: Placebo; Daily oral dose of two equal intakes, morning and evening, of Placebo in a double-blinded way for the 7-week Treatment Period
Experimental: Brivaracetam 20 mg/day; Brivaracetam 20 mg/day, 10 mg administered twice a day	Drug: Brivaracetam; Daily oral dose of two equal intakes, morning and evening, of Brivaracetam over the 7-week Treatment Period; Other Names: Briviact
Experimental: Brivaracetam 50 mg/day; Brivaracetam 50 mg/day, 25 mg administered twice a day	Drug: Brivaracetam; Daily oral dose of two equal intakes, morning and evening, of Brivaracetam over the 7-week Treatment Period; Other Names: Briviact
Experimental: Brivaracetam 5 mg/day; Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Drug: Brivaracetam; Daily oral dose of two equal intakes, morning and evening, of Brivaracetam over the 7-week Treatment Period; Other Names: Briviact

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial Onset Seizure Frequency Per Week During the 7-week Treatment Period	Calculated as 7-day partial onset seizure frequency.	During the 7-week Treatment Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Partial Onset Seizure Frequency Per Week (Type I) Over the 7-week Treatment Period	Calculated as 7-day seizure frequency during the 7-week Treatment Period - 7-day seizure frequency during the Baseline Period, divided by the 7-day seizure frequency during the Baseline Period with this quantity multiplied by 100. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline.	Baseline, during the 7-week Treatment Period
Seizure Frequency Per Week for All Seizures (Types I +II +III) Over the Treatment Period	Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or nonconvulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 7-day period.	During the 7-week Treatment Period
Absolute Change From Baseline in Seizure Frequency Per Week for Partial Onset Seizures (Type I) Over the Treatment Period	Calculated as 7-day Partial Onset Seizures (Type I) frequency during the 7-week Treatment Period 7-day seizure frequency during the Baseline Period. A negative value from Baseline indicates a decrease in partial seizure frequency from Baseline.	During the 7-week Treatment Period
Absolute Change From Baseline in Seizure Frequency Per Week for All Seizures (Types I + II + III) Over the Treatment Period	Calculated as 7-day seizure frequency during the 7-week Treatment Period 7-day seizure (Types I + II + III) frequency during the Baseline Period. A negative value from Baseline indicates a decrease in partial seizure frequency from Baseline.	During the 7-week Treatment Period
Percentage Change From Baseline in Seizure Frequency Per Week for All Seizures (Types I + II + III) Over the Treatment Period	Calculated as 7-day seizure frequency during the 7-week Treatment Period - 7-day seizure frequency during the Baseline Period, divided by the 7-day seizure frequency during the Baseline Period with this quantity multiplied by 100. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline.	During the 7-week Treatment Period
Responder Rate in Partial Onset Seizures (Type I) Over the Treatment Period	A responder was defined as a subject with a >= 50 % reduction in seizure frequency per week from the Baseline Period to the end of the Treatment Period.	During the 7-week Treatment Period
Percentage of Subjects With Categorized Response to the Treatment in Partial Onset Seizures (Type I) Over the Treatment Period	Categories of percentage reductions in seizures from baseline were as following: < -25 %; -25 % to <25 %; 25 % to <75 %; 75 % to <100 %; 100 %.	During the 7-week Treatment Period
Percentage of Subjects Who Are Seizure Free During the 7-week Treatment Period	A subject was considered seizure free, if no seizure was reported during the 7-week Treatment Period.	During the 7-week Treatment Period
Number of Seizure-free Days Per 4 Weeks	A day was considered seizure-free, if no seizure was reported during 24 hours.	Baseline, during the 7-week Treatment Period
Time to Nth (n= 1, 5, 10) Seizure During the 7-week Treatment Period	Number of days to first, fifth, and tenth seizure after baseline.	During the 7-week Treatment Period

Collaborators and Investigators

• Sponsor: UCB Pharma

Publications and helpful links

General Publications

• Toledo M, Whitesides J, Schiemann J, Johnson ME, Eckhardt K, McDonough B, Borghs S, Kwan P. Safety, tolerability, and seizure control during long-term treatment with adjunctive brivaracetam for partial-onset seizures. Epilepsia. 2016 Jul;57(7):1139-51. doi: 10.1111/epi.13416. Epub 2016 Jun 6.
• Bresnahan R, Panebianco M, Marson AG. Brivaracetam add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2022 Mar 14;3(3):CD011501. doi: 10.1002/14651858.CD011501.pub3.
• Brandt C, Klein P, Badalamenti V, Gasalla T, Whitesides J. Safety and tolerability of adjunctive brivaracetam in epilepsy: In-depth pooled analysis. Epilepsy Behav. 2020 Feb;103(Pt A):106864. doi: 10.1016/j.yebeh.2019.106864. Epub 2020 Jan 12.

Helpful Links

• FDA Safety Alerts and Recalls
• Product Information

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2005
• Primary Completion (Actual): June 29, 2006
• Study Completion (Actual): June 29, 2006

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Actual): October 2, 2018
• Last Update Submitted That Met QC Criteria: September 4, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: brivaracetam; Epilepsy: partial onset seizures
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Anticonvulsants; Brivaracetam
• Other Study ID Numbers: N01193