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

NCT00490035 | Completed Phase 3 Results

• 2 other identifiers: N012522006-006344-59
• Study Type: interventional
• Target: 399
• Locations: 12 countries
• Sites: 76

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

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 Secondarily Generalized Seizures.

  From Baseline to 12-week Treatment Period

Secondary Outcomes (22)

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

  From Baseline to 12-week Treatment Period

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

  From 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

  From 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

  From Baseline to 12-week Treatment Period

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

  From Baseline to 12-week Treatment Period

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Matching Placebo tablets administered twice a day

Other: Placebo

Brivaracetam 20 mg/day

EXPERIMENTAL

Brivaracetam 20 mg/day, 10 mg administered twice a day

Drug: Brivaracetam

Brivaracetam 50 mg/day

EXPERIMENTAL

Brivaracetam 50 mg/day, 25 mg administered twice a day

Drug: Brivaracetam

Brivaracetam 100 mg/day

EXPERIMENTAL

Brivaracetam 100 mg/day, 50 mg administered twice a day

Drug: Brivaracetam

Interventions

Placebo OTHER

Daily oral dose of two equal intakes, morning and evening, of Placebo in a double-blinded way for the 12-week Treatment Period

Placebo

Brivaracetam DRUG

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

Brivaracetam 20 mg/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 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

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 SA: lead

Study Sites (76)

13

Ghent, Belgium

Location

19

La Louvière, Belgium

Location

12

Liège, Belgium

Location

10

Sankt Vith, Belgium

Location

44

Kuopio, Finland

Location

41

Oulu, Finland

Location

42

Seinäjoki, Finland

Location

43

Tampere, Finland

Location

60

Angers, France

Location

56

Béthune, France

Location

62

Bron, France

Location

57

Dijon, France

Location

53

Lille, France

Location

52

Montpellier, France

Location

64

Nancy, France

Location

54

Paris, France

Location

51

Rennes, France

Location

61

Roanne, France

Location

55

Strasbourg, France

Location

76

Bad Berka, Germany

Location

73

Berlin, Germany

Location

79

Bernau, Germany

Location

78

Bielefeld, Germany

Location

74

Freiburg im Breisgau, Germany

Location

75

Kehl-Kork, Germany

Location

77

Mainz, Germany

Location

70

München, Germany

Location

72

Radeberg, Germany

Location

71

Ulm, Germany

Location

94

Budapest, Hungary

Location

90

Debrecen, Hungary

Location

92

Pécs, Hungary

Location

256

Bangalore, India

Location

257

Bangalore, India

Location

253

Hyderabad, India

Location

258

Jaipur, India

Location

255

Kolkata, India

Location

250

Lucknow, India

Location

259

Mumbai, India

Location

270

Pune, India

Location

251

Pune Maharashtra, India

Location

104

Bologna, Italy

Location

105

Foggia, Italy

Location

101

Perugia, Italy

Location

103

Roma, Italy

Location

107

Roma, Italy

Location

124

Breda, Netherlands

Location

125

The Hague, Netherlands

Location

122

Zwolle, Netherlands

Location

142

Bialystok, Poland

Location

143

Gdansk, Poland

Location

153

Grodzisk Mazowiecki, Poland

Location

147

Katowice, Poland

Location

151

Katowice, Poland

Location

141

Kielce, Poland

Location

150

Krakow, Poland

Location

148

Lodz, Poland

Location

144

Lublin, Poland

Location

152

Poznan, Poland

Location

146

Szczecin, Poland

Location

140

Warsaw, Poland

Location

145

Warsaw, Poland

Location

149

Warsaw, Poland

Location

187

Alcorcón, Spain

Location

181

Barcelona, Spain

Location

184

Donostia / San Sebastian, Spain

Location

182

Madrid, Spain

Location

183

Vigo, Spain

Location

185

Zaragoza, Spain

Location

201

Biel, Switzerland

Location

205

Geneva, Switzerland

Location

203

Sankt Gallen, Switzerland

Location

202

Tschugg, Switzerland

Location

204

Zurich, Switzerland

Location

223

Liverpool, United Kingdom

Location

224

Middlesbrough, United Kingdom

Location

Related Publications (17)

• 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.

  PMID: 24256083 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

• 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.

  PMID: 33461041 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: UCB 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

Study Record Dates

• First Submitted: June 21, 2007
• First Posted: June 22, 2007
• Study Start: September 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: July 21, 2022
• Results First Posted: April 13, 2016

Record last verified: 2022-07

Locations

FR (11); FI (4); DE (10); HU (3); IN (9); NL (3); ES (6); GB (2); PL (14); BE (4); IT (5); CH (5)