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

NCT00464269 | Completed Phase 3 Results

• 2 other identifiers: N012532006-006345-14
• Study Type: interventional
• Target: 400
• Locations: 5 countries
• Sites: 69

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.

Conditions

Epilepsy

Keywords

Epilepsy; Brivaracetam; Partial Onset Seizures, Adolescents & Adults

Outcome Measures

Primary Outcomes (1)

• Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period

  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)

  Baseline to 12-week Treatment Period

Secondary Outcomes (22)

• Responder Rate for Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period

  Baseline to 12-week Treatment Period

• All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period

  Baseline to 12-week Treatment Period

• Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week

  Baseline to 12-week Treatment Period

• Categorized Percentage Change From Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the 12-week Treatment Period

  Baseline to 12-week Treatment Period

• Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period

  Baseline to 12-week Treatment Period

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Brivaracetam 5 mg/day

EXPERIMENTAL

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

BRV 20mg/day

EXPERIMENTAL

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

BRV 50mg/day

EXPERIMENTAL

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

Interventions

Placebo OTHER

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

Placebo

Brivaracetam 25 mg DRUG

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

BRV 50mg/day

Brivaracetam 10 mg DRUG

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

BRV 20mg/day

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Pharma: lead

Study Sites (69)

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Fresno, California, United States

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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

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Chicago, Illinois, United States

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Springfield, Illinois, United States

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Wichita, Kansas, United States

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Lexington, Kentucky, United States

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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

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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

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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

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Salvador, Brazil

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São José do Rio Preto, Brazil

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São Paulo, Brazil

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Edmonton, Alberta, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Mexico City, Mexico City, Mexico

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Monterrey, Nuevo León, Mexico

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Aguascalientes, Mexico

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Chihuahua City, Mexico

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Mexico City, Mexico

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Monterrey, Mexico

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Nuevo León, Mexico

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San Luis Potosí City, Mexico

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Related Publications (16)

• 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.

  PMID: 24446953 RESULT

• 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.

  PMID: 27265725 RESULT

• 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.

  PMID: 27335114 RESULT

• 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.

  PMID: 27589414 RESULT

• 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.

  PMID: 28004320 RESULT

• 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.

  PMID: 27608437 RESULT

• 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.

  PMID: 28236727 RESULT

• 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.

  PMID: 27988967 RESULT

• 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.

  PMID: 28279891 RESULT

• 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.

  PMID: 29414542 RESULT

• 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.

  PMID: 29908435 RESULT

• 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.

  PMID: 32432339 RESULT

• 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.

  PMID: 34218211 RESULT

• 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.

  PMID: 35582748 RESULT

• 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.

  PMID: 35285519 DERIVED

• 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.

  PMID: 34155568 DERIVED

Related Links

• Product Information
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Epilepsy

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Clinical Trial Call Center
• Organization: UCB

+1 877 822 9493

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 19, 2007
• First Posted: April 23, 2007
• Study Start: September 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: January 1, 2009
• Last Updated: July 21, 2022
• Results First Posted: April 13, 2016

Record last verified: 2022-07

Locations

CA (4); AU (9); US (40); ME (8); BR (8)