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

NCT ID: NCT00464269

Last Updated: 2022-07-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-09-30

Study Completion Date

2009-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Epilepsy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

* Active Substance: Placebo
* Pharmaceutical Form: Film-coated tablet
* Concentration: 2.5 mg, 10 mg and 25 mg
* Route of Administration: Oral use

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.

Group Type EXPERIMENTAL

Brivaracetam 2.5 mg

Intervention Type DRUG

* Active Substance: Brivaracetam
* Pharmaceutical Form: Film-coated tablet
* Concentration: 2.5 mg
* Route of Administration: Oral use

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.

Group Type EXPERIMENTAL

Brivaracetam 10 mg

Intervention Type DRUG

* Active Substance: Brivaracetam
* Pharmaceutical Form: Film-coated tablet
* Concentration: 10 mg
* Route of Administration: Oral use

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.

Group Type EXPERIMENTAL

Brivaracetam 25 mg

Intervention Type DRUG

* Active Substance: Brivaracetam
* Pharmaceutical Form: Film-coated tablet
* Concentration: 25 mg
* Route of Administration: Oral use

Interventions

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Placebo

* Active Substance: Placebo
* Pharmaceutical Form: Film-coated tablet
* Concentration: 2.5 mg, 10 mg and 25 mg
* Route of Administration: Oral use

Intervention Type OTHER

Brivaracetam 2.5 mg

* Active Substance: Brivaracetam
* Pharmaceutical Form: Film-coated tablet
* Concentration: 2.5 mg
* Route of Administration: Oral use

Intervention Type DRUG

Brivaracetam 10 mg

* Active Substance: Brivaracetam
* Pharmaceutical Form: Film-coated tablet
* Concentration: 10 mg
* Route of Administration: Oral use

Intervention Type DRUG

Brivaracetam 25 mg

* Active Substance: Brivaracetam
* Pharmaceutical Form: Film-coated tablet
* Concentration: 25 mg
* Route of Administration: Oral use

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UCB Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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UCB Clinical Trial Call Center

Role: STUDY_DIRECTOR

+1 877 822 9493 (UCB)

Locations

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Phoenix, Arizona, United States

Site Status

Tucson, Arizona, United States

Site Status

Little Rock, Arkansas, United States

Site Status

Fresno, California, United States

Site Status

Los Angeles, California, United States

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Newport Beach, California, United States

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Sacramento, California, United States

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San Francisco, California, United States

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Washington D.C., District of Columbia, United States

Site Status

Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Chicago, Illinois, United States

Site Status

Springfield, Illinois, United States

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Wichita, Kansas, United States

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Lexington, Kentucky, United States

Site Status

Louisville, Kentucky, United States

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Baltimore, Maryland, United States

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Bethesda, Maryland, United States

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Burlington, Massachusetts, United States

Site Status

Detroit, Michigan, United States

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Grand Rapids, Michigan, United States

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Saint Paul, Minnesota, United States

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Tupelo, Mississippi, United States

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Chesterfield, Missouri, United States

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St Louis, Missouri, United States

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New York, New York, United States

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Rochester, New York, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Greenville, South Carolina, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Charlottesville, Virginia, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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Chatswood, New South Wales, Australia

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Randwick, New South Wales, Australia

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Woodville, South Australia, Australia

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Clayton, Victoria, Australia

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Fitzroy, Victoria, Australia

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Parkville, Victoria, Australia

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Adelaide, , Australia

Site Status

Fitzroy, , Australia

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West Heidelberg, , Australia

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Campinas, , Brazil

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Curitiba, , Brazil

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Florianópolis, , Brazil

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Porto Alegre, , Brazil

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Ribeirão Preto, , Brazil

Site Status

Salvador, , Brazil

Site Status

São José do Rio Preto, , Brazil

Site Status

São Paulo, , Brazil

Site Status

Edmonton, Alberta, Canada

Site Status

Greenfield Park, Quebec, Canada

Site Status

Montreal, Quebec, Canada

Site Status

Québec, Quebec, Canada

Site Status

Mexico City, Mexico City, Mexico

Site Status

Monterrey, Nuevo León, Mexico

Site Status

Aguascalientes, , Mexico

Site Status

Chihuahua City, , Mexico

Site Status

Mexico City, , Mexico

Site Status

Monterrey, , Mexico

Site Status

Nuevo León, , Mexico

Site Status

San Luis Potosí City, , Mexico

Site Status

Countries

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United States Australia Brazil Canada Mexico

References

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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.

Reference Type RESULT
PMID: 24446953 (View on PubMed)

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.

Reference Type RESULT
PMID: 27265725 (View on PubMed)

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.

Reference Type RESULT
PMID: 27335114 (View on PubMed)

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.

Reference Type RESULT
PMID: 27589414 (View on PubMed)

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.

Reference Type RESULT
PMID: 28004320 (View on PubMed)

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.

Reference Type RESULT
PMID: 27608437 (View on PubMed)

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.

Reference Type RESULT
PMID: 28236727 (View on PubMed)

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.

Reference Type RESULT
PMID: 27988967 (View on PubMed)

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.

Reference Type RESULT
PMID: 28279891 (View on PubMed)

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.

Reference Type RESULT
PMID: 29414542 (View on PubMed)

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.

Reference Type RESULT
PMID: 29908435 (View on PubMed)

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.

Reference Type RESULT
PMID: 32432339 (View on PubMed)

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.

Reference Type RESULT
PMID: 34218211 (View on PubMed)

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.

Reference Type RESULT
PMID: 35582748 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35285519 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34155568 (View on PubMed)

Related Links

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Other Identifiers

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2006-006345-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

N01253

Identifier Type: -

Identifier Source: org_study_id

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