Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma
ClinicalTrials.gov Identifier:
NCT00464269
First received: April 19, 2007
Last updated: March 14, 2016
Last verified: March 2016
  Purpose
This study will evaluate the efficacy and safety of Brivaracetam to support the submission file in the indication of adjunctive treatment in adolescents and adults with partial onset seizures.

Condition Intervention Phase
Epilepsy
Other: Placebo
Drug: Brivaracetam 2.5 mg
Drug: Brivaracetam 10 mg
Drug: Brivaracetam 25 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An International, Double-blind, Parallel-group, Placebo-controlled, Randomized Study: Evaluation of the Efficacy and Safety of Brivaracetam in Subjects (>= 16 to 70 Years Old) With Partial Onset Seizures

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    Partial (Type I) seizures can be classified into one of the following three groups:

    • Simple partial seizures
    • Complex partial seizures
    • Partial seizures evolving to generalized tonic-clonic convulsions.

    Partial Onset Seizure (POS) Frequency per week over the Treatment Period (TP) was calculated as:

    (Total Type I seizures over the TP)*7/(Total number of days with no missing seizure count in the TP)



Secondary Outcome Measures:
  • Responder Rate for Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The responder rate was presented as the number of responders and non-responders. A subject is a responder, if the subject has at least 50 % reduction in partial onset seizure frequency per week from Baseline to Treatment Period. Subjects with zero seizure frequency per week at Baseline were considered as non-responders.

  • All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    There are three different types of seizures:

    • Type I: Partial seizures
    • Type II: Generalized seizures
    • Type III: Unclassified epileptic seizures.

    All seizure frequency per week over Treatment Period (TP) was calculated as: (Total number of seizures over the TP)*7/(Total number of days with no missing seizure count in the TP)


  • Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    Percent change from Baseline was calculated as percent reduction by:

    (weekly seizure frequency Baseline - weekly seizure frequency Treatment)*100/(weekly seizure frequency Baseline).

    The higher the values for percent change in Partial Onset Seizure (POS) frequency, the higher the improvement from Baseline.


  • Categorized Percentage Change From Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the 12-week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    Subjects were classified in 1 of the following categories based on their percent reduction from Baseline to Treatment Period in Partial Onset Seizure (POS) frequency per week: <-25 %, -25 % to <25 %, 25 % to <50 %, 50 % to <75 %, 75 % to <100 %, and 100 %.

    Subjects having zero for Baseline seizure frequency per week were classified in the <-25 % category.


  • Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    Subjects were considered seizure free if their seizure counts for every day over the Treatment Period (TP) was zero and if they did not discontinue before the end of the TP. Seizure freedom rate was calculated as:

    (total number of seizure - free subjects in treatment group during TP)/(total number of evaluable Intent-To-Treat (ITT) subjects in treatment group)


  • Time to First Type I Seizure During the 12-week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The time to first Partial Onset Seizure (POS) in the Treatment Period is defined as the time between beginning of the Treatment Period and the date of occurrence of first Type I seizure. Subjects withdrawing during the Treatment Period before having a first Type I seizure were considered as having a first Type I seizure on the last day of their Treatment Period.

  • Time to Fifth Type I Seizure During the 12-week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The time to fifth Partial Onset Seizure (POS) in the Treatment Period is defined as the time between beginning of the Treatment Period and the date of occurrence of fifth Type I seizure. Subjects withdrawing during the Treatment Period before having a fifth Type I seizure were considered as having a fifth Type I seizure on the last day of their Treatment Period.

  • Time to Tenth Type I Seizure During the 12-week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The time to tenth Partial Onset Seizure (POS) in the Treatment Period is defined as the time between beginning of the Treatment Period and the date of occurrence of tenth Type I seizure. Subjects withdrawing during the Treatment Period before having a tenth Type I seizure were considered as having a tenth Type I seizure on the last day of their Treatment Period.

  • Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    This Outcome Measure was planned to be analyzed by pooling the present study with the other 2 Phase 3 studies (N01252 and N01254). If applicable, a detailed description of the pooled analysis will be provided in a separate analysis plan and results will be described in a separate report.

  • Change From Baseline to the 12-week Treatment Period in Total Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    The Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-items subscales - seizure worry (5 items), overall quality of life (2 items), emotional well-being (5 items), energy / fatigue (4 items), cognitive functioning (6 items), medication effects (3 items), and social function (5 items) - and a health status item.

    The subscale scores, the total score and the health status item score range from 0 to 100 and higher scores indicating better function.


  • Change From Baseline to the 12-week Treatment Period in Seizure Worry Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    The Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-items subscales - seizure worry (5 items), overall quality of life (2 items), emotional well-being (5 items), energy / fatigue (4 items), cognitive functioning (6 items), medication effects (3 items), and social function (5 items) - and a health status item.

    The subscale scores, the total score and the health status item score range from 0 to 100 and higher scores indicating better function.


  • Change From Baseline to the 12-week Treatment Period in Daily Activities / Social Functioning Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: Basline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    The Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-items subscales - seizure worry (5 items), overall quality of life (2 items), emotional well-being (5 items), energy / fatigue (4 items), cognitive functioning (6 items), medication effects (3 items), and social function (5 items) - and a health status item.

    The subscale scores, the total score and the health status item score range from 0 to 100 and higher scores indicating better function.


  • Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression. The HADS was developed as a self administered scale to assess the presence and severity of both anxiety and depression simultaneously. It consists of 14 items that are scored on a 4-point severity scale ranging from 0 to 3. A score per dimension was calculated with each score ranging from 0 to 21 and higher scores indicating higher depression / anxiety. A negative value in change from Baseline shows an improvement in HADS from Baseline.

  • Change From Baseline to the 12-week Treatment Period in Hospital Depression Score [ Time Frame: Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression. The HADS was developed as a self administered scale to assess the presence and severity of both anxiety and depression simultaneously. It consists of 14 items that are scored on a 4-point severity scale ranging from 0 to 3. A score per dimension was calculated with each score ranging from 0 to 21 and higher scores indicating higher depression / anxiety. A negative value in change from Baseline shows an improvement in HADS from Baseline.

  • Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit [ Time Frame: Baseline to Last Visit or Early Discontinuation Visit in the 12-week Treatment Period ] [ Designated as safety issue: No ]
    Patient's Global Evaluation Scale (P-GES) is a global assessment of the disease evolution which was performed using a seven-point scale (1= Marked worsening to 7 = Marked improvement) with the start of the study medication as the reference time point. The subject completed it by answering to the following: 'Overall, has there been a change in your seizures since the start of the study medication?'

  • Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit [ Time Frame: Baseline to Last Visit or Early Discontinuation Visit in the 12-week Treatment Period ] [ Designated as safety issue: No ]
    The Investigator's Global Evaluation Scale (I-GES) is a global assessment of the disease evolution which was performed using a seven-point scale (1 = Marked worsening to 7 = Marked improvement) with the start of the study medication as the reference time point. The investigator completed it by answering to the following: 'Assess the overall change in the severity of patient's illness, compared to start of study medication.'

  • Change From Baseline to the 12-week Treatment Period in Energy/Fatigue Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.

  • Change From Baseline to the 12-week Treatment Period in Emotional Well-Being Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.

  • Change From Baseline to the 12-week Treatment Period in Cognitive Functioning Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.

  • Change From Baseline to the 12-week Treatment Period in Medication Effects Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.

  • Change From Baseline to the 12-week Treatment Period in Overall Quality of Life Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.

  • Change From Baseline to the 12-week Treatment Period in Health Status of Life Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) Score [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.


Enrollment: 400
Study Start Date: September 2007
Study Completion Date: January 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Matching Placebo tablets administered twice a day. Daily oral dose of two equal intakes, morning and evening, of Placebo in a double-blinded way for the 12-week Treatment Period.
Other: Placebo
  • Active Substance: Placebo
  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 2.5 mg, 10 mg and 25 mg
  • Route of Administration: Oral use
Experimental: Brivaracetam 5 mg/day
Brivaracetam 5 mg/day, 2.5 mg administered twice a day. Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 5 mg /day in a double-blinded way for the 12-week Treatment Period.
Drug: Brivaracetam 2.5 mg
  • Active Substance: Brivaracetam
  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 2.5 mg
  • Route of Administration: Oral use
Experimental: BRV 20mg/day
Brivaracetam 20 mg/day, 10 mg administered twice a day. Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 20 mg /day in a double-blinded way for the 12-week Treatment Period.
Drug: Brivaracetam 10 mg
  • Active Substance: Brivaracetam
  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 10 mg
  • Route of Administration: Oral use
Experimental: BRV 50mg/day
Brivaracetam 50 mg/day, 25 mg administered twice a day. Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 50 mg /day, in a double-blinded way for the 12-week Treatment Period.
Drug: Brivaracetam 25 mg
  • Active Substance: Brivaracetam
  • Pharmaceutical Form: Film-coated tablet
  • Concentration: 25 mg
  • Route of Administration: Oral use

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects were 16 to 70 years, both inclusive. Subjects under 18 years of age were only included where legally permitted and ethically accepted
  • Subjects with well-characterized focal epilepsy or epileptic syndrome according to the International League Against Epilepsy (ILAE) classification
  • Subjects had a history of partial onset seizures (POS) whether or not secondarily generalized (Type I seizures according to the ILAE classification)
  • Subjects had at least 2 POS whether or not secondarily generalized per month during the 3 months preceding Visit 1 (V1)
  • Subjects had at least 8 POS whether or not secondarily generalized during the 8-Week Baseline Period
  • Subjects were uncontrolled while treated by 1 to 2 permitted concomitant antiepileptic drug(s) (AEDs). Vagal nerve stimulation (VNS) was allowed and was not counted as a concomitant AED

Exclusion Criteria:

  • History or presence of seizures occurring only in clusters (too frequently or indistinctly separated to be reliably counted) before Visit 3
  • History or presence of status epilepticus during the year preceding Visit 1 or during Baseline
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00464269

  Show 70 Study Locations
Sponsors and Collaborators
UCB Pharma
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Publications:
Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT00464269     History of Changes
Other Study ID Numbers: N01253  2006-006345-14 
Study First Received: April 19, 2007
Results First Received: March 14, 2016
Last Updated: March 14, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Brazil: National Health Surveillance Agency
Mexico: Federal Commission for Protection Against Health Risks
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by UCB Pharma:
Epilepsy
Brivaracetam
Partial Onset Seizures, Adolescents & Adults

Additional relevant MeSH terms:
Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on July 24, 2016