Clinical trial NCT00464269: Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Epilepsy
Brivaracetam
Partial Onset Seizures, Adolescents & Adults
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2007-04-23
Enrollment: 400
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
Secondary outcomes:
measure: Responder Rate for Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
measure: All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
measure: Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week
timeFrame: Baseline to 12-week Treatment Period
measure: Categorized Percentage Change From Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the 12-week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
measure: Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
measure: Time to First Type I Seizure During the 12-week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
measure: Time to Fifth Type I Seizure During the 12-week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
measure: Time to Tenth Type I Seizure During the 12-week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
measure: Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period
timeFrame: Baseline to 12-week Treatment Period
measure: 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
timeFrame: Baseline to 12-week Treatment Period
measure: 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
timeFrame: Baseline to 12-week Treatment Period
measure: 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
timeFrame: Baseline to 12-week Treatment Period
measure: Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score
timeFrame: Baseline to 12-week Treatment Period
measure: Change From Baseline to the 12-week Treatment Period in Hospital Depression Score
timeFrame: Baseline to 12-week Treatment Period
measure: Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit
timeFrame: Baseline to Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
measure: Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit
timeFrame: Baseline to Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
measure: 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
timeFrame: From Baseline to 12-week Treatment Period
measure: 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
timeFrame: From Baseline to 12-week Treatment Period
measure: 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
timeFrame: From Baseline to 12-week Treatment Period
measure: 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
timeFrame: From Baseline to 12-week Treatment Period
measure: 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
timeFrame: From Baseline to 12-week Treatment Period
measure: 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
timeFrame: From Baseline to 12-week Treatment Period
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Fresno
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Burlington
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Saint Paul
country: United States
state: Minnesota
city: Tupelo
country: United States
state: Mississippi
city: Chesterfield
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Charlottesville
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Chatswood
country: Australia
state: New South Wales
city: Randwick
country: Australia
state: New South Wales
city: Woodville
country: Australia
state: South Australia
city: Clayton
country: Australia
state: Victoria
city: Fitzroy
country: Australia
state: Victoria
city: Parkville
country: Australia
state: Victoria
city: Adelaide
country: Australia
city: Fitzroy
country: Australia
city: West Heidelberg
country: Australia
city: Campinas
country: Brazil
city: Curitiba
country: Brazil
city: Florianópolis
country: Brazil
city: Porto Alegre
country: Brazil
city: Ribeirao Preto
country: Brazil
city: Salvador
country: Brazil
city: Sao Jose do Rio Preto
country: Brazil
city: Sao Paulo
country: Brazil
city: São Paulo
country: Brazil
city: Edmonton
country: Canada
state: Alberta
city: Greenfield Park
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Quebec City
country: Canada
state: Quebec
city: Mexico
country: Mexico
state: DF
city: Monterrey
country: Mexico
state: NL
city: Aguascalientes
country: Mexico
city: Chihuahua
country: Mexico
city: Mexico DF
country: Mexico
city: Monterrey
country: Mexico
city: Nuevo León
country: Mexico
city: San Luis Potosi
country: Mexico
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Biton V, Berkovic SF, Abou-Khalil B, Sperling MR, Johnson ME, Lu S. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 2014 Jan;55(1):57-66. doi: 10.1111/epi.12433. Epub 2013 Nov 8.
citation: 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.
citation: Ben-Menachem E, Mameniskiene R, Quarato PP, Klein P, Gamage J, Schiemann J, Johnson ME, Whitesides J, McDonough B, Eckhardt K. Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies. Neurology. 2016 Jul 19;87(3):314-23. doi: 10.1212/WNL.0000000000002864. Epub 2016 Jun 22.
citation: Brodie MJ, Whitesides J, Schiemann J, D'Souza J, Johnson ME. Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies. Epilepsy Res. 2016 Nov;127:114-118. doi: 10.1016/j.eplepsyres.2016.08.018. Epub 2016 Aug 18.
citation: Mukuria C, Young T, Keetharuth A, Borghs S, Brazier J. Sensitivity and responsiveness of the EQ-5D-3L in patients with uncontrolled focal seizures: an analysis of Phase III trials of adjunctive brivaracetam. Qual Life Res. 2017 Mar;26(3):749-759. doi: 10.1007/s11136-016-1483-3. Epub 2016 Dec 21.
citation: Moseley BD, Sperling MR, Asadi-Pooya AA, Diaz A, Elmouft S, Schiemann J, Whitesides J. Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonic-clonic seizures: Pooled results from three Phase III studies. Epilepsy Res. 2016 Nov;127:179-185. doi: 10.1016/j.eplepsyres.2016.09.003. Epub 2016 Sep 3.
citation: Brandt C, Borghs S, Elmoufti S, Mueller K, Townsend R, de la Loge C. Health-related quality of life in double-blind Phase III studies of brivaracetam as adjunctive therapy of focal seizures: A pooled, post-hoc analysis. Epilepsy Behav. 2017 Apr;69:80-85. doi: 10.1016/j.yebeh.2016.11.031. Epub 2017 Feb 23.
citation: Klein P, Johnson ME, Schiemann J, Whitesides J. Time to onset of sustained >/=50% responder status in patients with focal (partial-onset) seizures in three phase III studies of adjunctive brivaracetam treatment. Epilepsia. 2017 Feb;58(2):e21-e25. doi: 10.1111/epi.13631. Epub 2016 Dec 18.
citation: Asadi-Pooya AA, Sperling MR, Chung S, Klein P, Diaz A, Elmoufti S, Schiemann J, Whitesides J. Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: A post-hoc study. Epilepsy Res. 2017 Mar;131:70-75. doi: 10.1016/j.eplepsyres.2017.02.007. Epub 2017 Feb 27.
citation: Benbadis S, Klein P, Schiemann J, Diaz A, Elmoufti S, Whitesides J. Efficacy, safety, and tolerability of brivaracetam with concomitant lamotrigine or concomitant topiramate in pooled Phase III randomized, double-blind trials: A post-hoc analysis. Epilepsy Behav. 2018 Mar;80:129-134. doi: 10.1016/j.yebeh.2017.12.024. Epub 2018 Feb 3.
citation: Brodie MJ, Fakhoury T, McDonough B, Colson AO, Stockis A, Elmoufti S, Whitesides J. Brivaracetam-induced elevation of carbamazepine epoxide levels: A post-hoc analysis from the clinical development program. Epilepsy Res. 2018 Sep;145:55-62. doi: 10.1016/j.eplepsyres.2018.06.002. Epub 2018 Jun 4.
citation: Klein P, Laloyaux C, Elmoufti S, Gasalla T, Martin MS. Time course of 75%-100% efficacy response of adjunctive brivaracetam. Acta Neurol Scand. 2020 Aug;142(2):175-180. doi: 10.1111/ane.13287. Epub 2020 Jun 9.
citation: Moseley BD, Dimova S, Elmoufti S, Laloyaux C, Asadi-Pooya AA. Long-term efficacy and tolerability of adjunctive brivaracetam in adults with focal to bilateral tonic-clonic (secondary generalized) seizures: Post hoc pooled analysis. Epilepsy Res. 2021 Oct;176:106694. doi: 10.1016/j.eplepsyres.2021.106694. Epub 2021 Jun 24.
citation: Ryvlin P, Dimova S, Elmoufti S, Floricel F, Laloyaux C, Nondonfaz X, Biton V. Tolerability and efficacy of adjunctive brivaracetam in adults with focal seizures by concomitant antiseizure medication use: Pooled results from three phase 3 trials. Epilepsia. 2022 Aug;63(8):2024-2036. doi: 10.1111/epi.17304. Epub 2022 Jun 10.
citation: 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.
citation: Lee SK, Heo K, Kim SE, Lee SA, Elmoufti S, Laloyaux C, Hur B. Effect of Number of Previous Antiseizure Medications on Efficacy and Tolerability of Adjunctive Brivaracetam for Uncontrolled Focal Seizures: Post Hoc Analysis. Adv Ther. 2021 Jul;38(7):4082-4099. doi: 10.1007/s12325-021-01816-5. Epub 2021 Jun 21.