Clinical trial NCT00490035: Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Epilepsy
Brivaracetam
Partial Onset Seizures
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2007-06-22
Enrollment: 399
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 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

Primary outcomes:
measure: Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period
timeFrame: From Baseline to 12-week Treatment Period
Secondary outcomes:
measure: Responder Rate for Partial Onset Seizures (Type I) Frequency Per Week Over the 12-week Treatment Period
timeFrame: From Baseline to 12-week Treatment Period
measure: All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period
timeFrame: From 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: From 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: From Baseline to 12-week Treatment Period
measure: Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period
timeFrame: From Baseline to 12-week Treatment Period
measure: Time to First Type I Seizure During the 12-week Treatment Period
timeFrame: From Baseline to 12-week Treatment Period
measure: Time to Fifth Type I Seizure During the 12-week Treatment Period
timeFrame: From Baseline to 12-week Treatment Period
measure: Time to Tenth Type I Seizure During the 12-week Treatment Period
timeFrame: From 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: From 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: From 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: From 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: From Baseline to 12-week Treatment Period
measure: Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score
timeFrame: From Baseline to 12-week Treatment Period
measure: Change From Baseline to the 12-week Treatment Period in Hospital Depression Score
timeFrame: From Baseline to 12-week Treatment Period
measure: Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit
timeFrame: 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: 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: Gent
country: Belgium
facility: 13
city: La Louviere
country: Belgium
facility: 19
city: Liege
country: Belgium
facility: 12
city: Saint-Vith
country: Belgium
facility: 10
city: Kuopio
country: Finland
facility: 44
city: Oulu
country: Finland
facility: 41
city: Seinajoki
country: Finland
facility: 42
city: Tampere
country: Finland
facility: 43
city: Angers Cedex 9
country: France
facility: 60
city: Bethune
country: France
facility: 56
city: Bron
country: France
facility: 62
city: Dijon
country: France
facility: 57
city: Lille
country: France
facility: 53
city: Montpellier Cedex
country: France
facility: 52
city: Nancy
country: France
facility: 64
city: Paris
country: France
facility: 54
city: Rennes
country: France
facility: 51
city: Roanne
country: France
facility: 61
city: Strasbourg
country: France
facility: 55
city: Bad Berka
country: Germany
facility: 76
city: Berlin
country: Germany
facility: 73
city: Bernau
country: Germany
facility: 79
city: Bielefeld
country: Germany
facility: 78
city: Freiburg
country: Germany
facility: 74
city: Kehl-Kork
country: Germany
facility: 75
city: Mainz
country: Germany
facility: 77
city: Munchen
country: Germany
facility: 70
city: Radeberg
country: Germany
facility: 72
city: Ulm
country: Germany
facility: 71
city: Budapest
country: Hungary
facility: 94
city: Debrecen
country: Hungary
facility: 90
city: Pecs
country: Hungary
facility: 92
city: Bangalore
country: India
facility: 256
city: Bangalore
country: India
facility: 257
city: Hyderabad
country: India
facility: 253
city: Jaipur
country: India
facility: 258
city: Kolkata
country: India
facility: 255
city: Lucknow
country: India
facility: 250
city: Mumbai
country: India
facility: 259
city: Pune Maharashtra
country: India
facility: 251
city: Pune
country: India
facility: 270
city: Bologna
country: Italy
facility: 104
city: Foggia
country: Italy
facility: 105
city: Perugia
country: Italy
facility: 101
city: Roma
country: Italy
facility: 103
city: Roma
country: Italy
facility: 107
city: Breda
country: Netherlands
facility: 124
city: Den Haag
country: Netherlands
facility: 125
city: Zwolle
country: Netherlands
facility: 122
city: Bialystok
country: Poland
facility: 142
city: Gdansk
country: Poland
facility: 143
city: Grodzisk Mazowiecki
country: Poland
facility: 153
city: Katowice
country: Poland
facility: 147
city: Katowice
country: Poland
facility: 151
city: Kielce
country: Poland
facility: 141
city: Krakow
country: Poland
facility: 150
city: Lodz
country: Poland
facility: 148
city: Lublin
country: Poland
facility: 144
city: Poznan
country: Poland
facility: 152
city: Szczecin
country: Poland
facility: 146
city: Warsaw
country: Poland
facility: 145
city: Warszawa
country: Poland
facility: 140
city: Warszawa
country: Poland
facility: 149
city: Alcorcon
country: Spain
facility: 187
city: Barcelona
country: Spain
facility: 181
city: Madrid
country: Spain
facility: 182
city: San Sebastian
country: Spain
facility: 184
city: Vigo
country: Spain
facility: 183
city: Zaragoza
country: Spain
facility: 185
city: Biel
country: Switzerland
facility: 201
city: Geneve
country: Switzerland
facility: 205
city: St Gallen
country: Switzerland
facility: 203
city: Tschugg
country: Switzerland
facility: 202
city: Zürich
country: Switzerland
facility: 204
city: Liverpool
country: United Kingdom
facility: 223
city: Middlesborough
country: United Kingdom
facility: 224
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Ryvlin P, Werhahn KJ, Blaszczyk B, Johnson ME, Lu S. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014 Jan;55(1):47-56. doi: 10.1111/epi.12432. Epub 2013 Oct 28.
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.
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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.
citation: Ben-Menachem E, Baulac M, Hong SB, Cleveland JM, Reichel C, Schulz AL, Wagener G, Brandt C. Safety, tolerability, and efficacy of brivaracetam as adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease: An open-label, long-term follow-up trial. Epilepsy Res. 2021 Feb;170:106526. doi: 10.1016/j.eplepsyres.2020.106526. Epub 2020 Dec 4.