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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 ( UCB Pharma SA )
ClinicalTrials.gov Identifier:
NCT00490035
First received: June 21, 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
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: A Multi-center, 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: From 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 Secondarily Generalized Seizures.


Secondary Outcome Measures:
  • Responder Rate for Partial Onset Seizures (Type I) Frequency Per Week Over the 12-week Treatment Period [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    Responders are those subjects with at least 50 % reduction from Baseline to Treatment Period in Partial Onset Seizure frequency per week.

    The Responder Rate for Partial Onset Seizures (Type I) is the proportion of subjects who have a >= 50 % reduction in seizure frequency per week from Baseline.


  • All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    There are three types of Epilepsy: Partial Epilepsies (Type I), Generalized Epilepsies (Type II) and uncertain classification of Epilepsies (Type III).

  • Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The percent change from Baseline was computed as: Weekly Seizure Frequency (Treatment) - Weekly Seizure Frequency (Baseline) / Weekly Seizure Frequency (Baseline) * 100. Negative values indicate a reduction from Baseline with higher negative values showing higher reduction.

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

    The categories are:

    • <= 25 %
    • - 25 % to < 25 %
    • 25 % to < 50 %
    • 50 % to < 75 %
    • 75 % to < 100 %
    • 100 %

  • Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period [ Time Frame: From 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 entire Treatment Period was zero and if they completed the Treatment Period.

  • Time to First Type I Seizure During the 12-week Treatment Period [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The time to first Type I Seizure during the 12-week Treatment Period was measured in days.

  • Time to Fifth Type I Seizure During the 12-week Treatment Period [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The time to Fifth Type I Seizure during the 12-week Treatment Period was measured in days.

  • Time to Tenth Type I Seizure During the 12-week Treatment Period [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]
    The time to tenth Type I Seizure during the 12-week Treatment Period was measured in days.

  • Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period. [ Time Frame: From Baseline to 12-week Treatment Period ] [ Designated as safety issue: No ]

    Reduction of Type IC/Type I Seizure frequency ratio from Baseline to the 12- week Treatment Period.

    This variable was not analyzed and no results are available.


  • 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: 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 Seizure Worry 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 Daily Activities/Social 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 Hospital Anxiety Score [ Time Frame: From 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 simultaneously. The HADS was developed as a self-administered scale that has been designed to assess the presence and severity of both anxiety and depression. 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. Negative values in Change from Baseline indicate a decrease of HADS from Baseline to Treatment Period.

  • Change From Baseline to the 12-week Treatment Period in Hospital Depression Score [ Time Frame: From 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 simultaneously. The HADS was developed as a self-administered scale that has been designed to assess the presence and severity of both anxiety and depression. 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. Negative values in Change from Baseline indicate a decrease of HADS from Baseline to Treatment Period.

  • Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit [ Time Frame: Last Visit or Early Discontinuation Visit in the 12-week Treatment Period ] [ Designated as safety issue: No ]
    The 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 not mentally impaired had to complete it by answering the following question: "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: 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 reference time point. The Investigator was to complete it by answering the following question: "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: 399
Study Start Date: September 2007
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 12-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 20 mg /day in a double-blinded way for the 12-week Treatment Period
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 50 mg /day in a double-blinded way for the 12-week Treatment Period.
Experimental: Brivaracetam 100 mg/day
Brivaracetam 100 mg/day, 50 mg administered twice a day
Drug: Brivaracetam
Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 100 mg /day in a double-blinded way for the 12-week Treatment Period.

  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 from 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
  • 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 drugs (AEDs). Vagal nerve stimulation 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: NCT00490035

  Show 76 Study Locations
Sponsors and Collaborators
UCB Pharma SA
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Publications:
Responsible Party: UCB Pharma SA
ClinicalTrials.gov Identifier: NCT00490035     History of Changes
Other Study ID Numbers: N01252  2006-006344-59 
Study First Received: June 21, 2007
Results First Received: March 14, 2016
Last Updated: March 14, 2016
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Medicines Evaluation Board (MEB)
Poland: Ministry of Health
Switzerland: Swissmedic
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India

Keywords provided by UCB Pharma:
Epilepsy
Brivaracetam
Partial Onset Seizures

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 December 06, 2016