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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00464269




Registration number
NCT00464269
Ethics application status
Date submitted
19/04/2007
Date registered
23/04/2007
Date last updated
21/07/2022

Titles & IDs
Public title
Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures
Scientific 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
Secondary ID [1] 0 0
2006-006345-14
Secondary ID [2] 0 0
N01253
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Other interventions - Placebo
Treatment: Drugs - Brivaracetam 2.5 mg
Treatment: Drugs - Brivaracetam 10 mg
Treatment: Drugs - Brivaracetam 25 mg

Placebo comparator: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.


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

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

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

Treatment: Drugs: Brivaracetam 25 mg
* Active Substance: Brivaracetam
* Pharmaceutical Form: Film-coated tablet
* Concentration: 25 mg
* Route of Administration: Oral use
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period
Timepoint [1] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [1] 0 0
Responder Rate for Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period
Timepoint [1] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [2] 0 0
All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period
Timepoint [2] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [3] 0 0
Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week
Timepoint [3] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [4] 0 0
Categorized Percentage Change From Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the 12-week Treatment Period
Timepoint [4] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [5] 0 0
Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period
Timepoint [5] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [6] 0 0
Time to First Type I Seizure During the 12-week Treatment Period
Timepoint [6] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [7] 0 0
Time to Fifth Type I Seizure During the 12-week Treatment Period
Timepoint [7] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [8] 0 0
Time to Tenth Type I Seizure During the 12-week Treatment Period
Timepoint [8] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [9] 0 0
Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period
Timepoint [9] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [13] 0 0
Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score
Timepoint [13] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [14] 0 0
Change From Baseline to the 12-week Treatment Period in Hospital Depression Score
Timepoint [14] 0 0
Baseline to 12-week Treatment Period
Secondary outcome [15] 0 0
Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit
Timepoint [15] 0 0
Baseline to Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
Secondary outcome [16] 0 0
Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit
Timepoint [16] 0 0
Baseline to Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
Secondary outcome [17] 0 0
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
Timepoint [17] 0 0
From Baseline to 12-week Treatment Period
Secondary outcome [18] 0 0
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
Timepoint [18] 0 0
From Baseline to 12-week Treatment Period
Secondary outcome [19] 0 0
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
Timepoint [19] 0 0
From Baseline to 12-week Treatment Period
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
From Baseline to 12-week Treatment Period
Secondary outcome [21] 0 0
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
Timepoint [21] 0 0
From Baseline to 12-week Treatment Period
Secondary outcome [22] 0 0
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
Timepoint [22] 0 0
From Baseline to 12-week Treatment Period

Eligibility
Key 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
Minimum age
16 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2009
Sample size
Target
Accrual to date
Final
400
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
- Chatswood
Recruitment hospital [2] 0 0
- Randwick
Recruitment hospital [3] 0 0
- Woodville
Recruitment hospital [4] 0 0
- Clayton
Recruitment hospital [5] 0 0
- Fitzroy
Recruitment hospital [6] 0 0
- Parkville
Recruitment hospital [7] 0 0
- Adelaide
Recruitment hospital [8] 0 0
- West Heidelberg
Recruitment postcode(s) [1] 0 0
- Chatswood
Recruitment postcode(s) [2] 0 0
- Randwick
Recruitment postcode(s) [3] 0 0
- Woodville
Recruitment postcode(s) [4] 0 0
- Clayton
Recruitment postcode(s) [5] 0 0
- Fitzroy
Recruitment postcode(s) [6] 0 0
- Parkville
Recruitment postcode(s) [7] 0 0
- Adelaide
Recruitment postcode(s) [8] 0 0
- West Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Mississippi
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Washington
Country [25] 0 0
United States of America
State/province [25] 0 0
Wisconsin
Country [26] 0 0
Brazil
State/province [26] 0 0
Campinas
Country [27] 0 0
Brazil
State/province [27] 0 0
Curitiba
Country [28] 0 0
Brazil
State/province [28] 0 0
Florianópolis
Country [29] 0 0
Brazil
State/province [29] 0 0
Porto Alegre
Country [30] 0 0
Brazil
State/province [30] 0 0
Ribeirao Preto
Country [31] 0 0
Brazil
State/province [31] 0 0
Salvador
Country [32] 0 0
Brazil
State/province [32] 0 0
Sao Jose do Rio Preto
Country [33] 0 0
Brazil
State/province [33] 0 0
Sao Paulo
Country [34] 0 0
Brazil
State/province [34] 0 0
São Paulo
Country [35] 0 0
Canada
State/province [35] 0 0
Alberta
Country [36] 0 0
Canada
State/province [36] 0 0
Quebec
Country [37] 0 0
Mexico
State/province [37] 0 0
DF
Country [38] 0 0
Mexico
State/province [38] 0 0
NL
Country [39] 0 0
Mexico
State/province [39] 0 0
Aguascalientes
Country [40] 0 0
Mexico
State/province [40] 0 0
Chihuahua
Country [41] 0 0
Mexico
State/province [41] 0 0
Mexico DF
Country [42] 0 0
Mexico
State/province [42] 0 0
Monterrey
Country [43] 0 0
Mexico
State/province [43] 0 0
Nuevo León
Country [44] 0 0
Mexico
State/province [44] 0 0
San Luis Potosi

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
UCB Pharma
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00464269
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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. Erratum In: Epilepsy Res. 2017 Nov;137:165-166. doi: 10.1016/j.eplepsyres.2017.04.019.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
UCB Clinical Trial Call Center
Address 0 0
+1 877 822 9493 (UCB)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00464269