EpilepsyPhase 3NCT00490035
Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures
A Phase 3 study testing Brivaracetam in people with Epilepsy, run by UCB Pharma SA at 76 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Epilepsy
- What is being tested?
- Brivaracetam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 399 participants
- Where
- 76 sitesin 12 countries
- Study dates
- Sep 2007to Feb 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
76 sites in 12 countries.
76 sites in 12 countries
Poland14 sites
142
Bialystok
143
Gdansk
153
Grodzisk Mazowiecki
147
Katowice
151
Katowice
141
Kielce
150
Krakow
148
Lodz
144
Lublin
152
Poznan
146
Szczecin
140
Warsaw
145
Warsaw
149
Warsaw
France11 sites
60
Angers
56
Béthune
62
Bron
57
Dijon
53
Lille
52
Montpellier
64
Nancy
54
Paris
51
Rennes
61
Roanne
55
Strasbourg
Germany10 sites
76
Bad Berka
73
Berlin
79
Bernau
78
Bielefeld
74
Freiburg im Breisgau
75
Kehl-Kork
77
Mainz
70
München
72
Radeberg
71
Ulm
India9 sites
256
Bangalore
257
Bangalore
253
Hyderabad
258
Jaipur
255
Kolkata
250
Lucknow
259
Mumbai
270
Pune
251
Pune Maharashtra
Spain6 sites
187
Alcorcón
181
Barcelona
184
Donostia / San Sebastian
182
Madrid
183
Vigo
185
Zaragoza
Switzerland5 sites
201
Biel
205
Geneva
203
Sankt Gallen
202
Tschugg
204
Zurich
About this study
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.
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
- Being tested
- Placebo, Brivaracetam
- Keywords
- Epilepsy, Brivaracetam, Partial Onset Seizures
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Daily oral dose of two equal intakes, morning and evening, of Placebo in a double-blinded way for the 12-week Treatment Period
BrivaracetamDrug
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
BrivaracetamDrug
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.
BrivaracetamDrug
Daily oral dose of two equal intakes, morning and evening, of Brivaracetam 100 mg /day in a double-blinded way for the 12-week Treatment Period.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching Placebo tablets administered twice a day Receives: Other: Placebo |
| Brivaracetam 20 mg/day | Experimental | Brivaracetam 20 mg/day, 10 mg administered twice a day Receives: Drug: Brivaracetam |
| Brivaracetam 50 mg/day | Experimental | Brivaracetam 50 mg/day, 25 mg administered twice a day Receives: Drug: Brivaracetam |
| Brivaracetam 100 mg/day | Experimental | Brivaracetam 100 mg/day, 50 mg administered twice a day Receives: Drug: Brivaracetam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Responders are those subjects with at least 50 % reduction from Baseline to Treatment Period in Partial Onset Seizure frequency per week.
The Responder Rate for Partial Onset Seizures (Type I) is the proportion of subjects who have a >= 50 % reduction in seizure frequency per week from Baseline.
Measured: From Baseline to 12-week Treatment Period
All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period
There are three types of Epilepsy: Partial Epilepsies (Type I), Generalized Epilepsies (Type II) and uncertain classification of Epilepsies (Type III).
Measured: 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
The percent change from Baseline was computed as: Weekly Seizure Frequency (Treatment) - Weekly Seizure Frequency (Baseline) / Weekly Seizure Frequency (Baseline) * 100. Negative values indicate a reduction from Baseline with higher negative values showing higher reduction.
Measured: 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
The categories are:
- <= 25 %
- - 25 % to < 25 %
- 25 % to < 50 %
- 50 % to < 75 %
- 75 % to < 100 %
- 100 %
Measured: From Baseline to 12-week Treatment Period
Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period
Subjects were considered seizure free if their seizure counts for every day over the entire Treatment Period was zero and if they completed the Treatment Period.
Measured: From Baseline to 12-week Treatment Period
Time to First Type I Seizure During the 12-week Treatment Period
The time to first Type I Seizure during the 12-week Treatment Period was measured in days.
Measured: From Baseline to 12-week Treatment Period
Time to Fifth Type I Seizure During the 12-week Treatment Period
The time to Fifth Type I Seizure during the 12-week Treatment Period was measured in days.
Measured: From Baseline to 12-week Treatment Period
Time to Tenth Type I Seizure During the 12-week Treatment Period
The time to tenth Type I Seizure during the 12-week Treatment Period was measured in days.
Measured: From Baseline to 12-week Treatment Period
Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period.
The type IC/Type I seizure frequency ratio is represented by the percentage of subjects having a reduction in the ratio of Type IC seizure frequency over Type IA, IB, and IC seizure frequency from Baseline to Treatment Period.
Measured: From Baseline to 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score
The Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression simultaneously. The HADS was developed as a self-administered scale that has been designed to assess the presence and severity of both anxiety and depression. It consists of 14 items that are scored on a 4-point severity scale ranging from 0 to 3. A score per dimension was calculated with each score ranging from 0 to 21 and higher scores indicating higher depression / anxiety. Negative values in Change from Baseline indicate a decrease of HADS from Baseline to Treatment Period.
Measured: From Baseline to 12-week Treatment Period
Change From Baseline to the 12-week Treatment Period in Hospital Depression Score
The Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety and depression simultaneously. The HADS was developed as a self-administered scale that has been designed to assess the presence and severity of both anxiety and depression. It consists of 14 items that are scored on a 4-point severity scale ranging from 0 to 3. A score per dimension was calculated with each score ranging from 0 to 21 and higher scores indicating higher depression / anxiety. Negative values in Change from Baseline indicate a decrease of HADS from Baseline to Treatment Period.
Measured: From Baseline to 12-week Treatment Period
Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit
The Patient's Global Evaluation Scale (P-GES) is a global assessment of the disease evolution which was performed using a seven-point scale (1 = Marked worsening to 7 = Marked improvement) with the start of the study medication as the reference time point. The subject not mentally impaired had to complete it by answering the following question: "Overall, has there been a change in your seizures since the start of the study medication?"
Measured: Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit
The Investigator's Global Evaluation Scale (I-GES) is a global assessment of the disease evolution which was performed using a seven-point scale (1 = Marked worsening to 7 = Marked improvement), with the start of the study medication as reference time point. The Investigator was to complete it by answering the following question: "Assess the Overall change in the severity of patient's illness, compared to start of study medication."
Measured: Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
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
The QOLIE-31-P is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into seven multi-item subscales - Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-Being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items) - and a Health Status item. The subscale scores, the Total score and the Health Status item score are calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. A positive value in Change from Baseline indicates an improvement from Baseline.
Measured: From Baseline to 12-week Treatment Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2007 (estimated)
- Study startSep 2007
- Primary completionFeb 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 399 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB Pharma SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- UCB Clinical Trial Call Center, Study director, +1 877 822 9493 (UCB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00490035
- Sponsor's protocol ID
- N01252
- Other IDs
- 2006-006344-59
- Status last verified
- Jul 2022
- First submitted
- 21 Jun 2007
- Last updated
- 21 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24256083Toledo 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.
PubMed 27265725Ben-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.
PubMed 27335114Brodie 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.
PubMed 27589414Mukuria 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.
PubMed 28004320Moseley 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.
PubMed 27608437Brandt 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.
PubMed 28236727Klein 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.
PubMed 27988967Asadi-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.
PubMed 28279891Benbadis 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.
PubMed 29414542Brodie 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.
PubMed 29908435Klein 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.
PubMed 32432339Moseley 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.
PubMed 34218211Ryvlin 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.
PubMed 35582748Meador KJ, Dimova S, Bourikas D, Elmoufti S, Floricel F, Laloyaux C, Moseley B, Nondonfaz X, Klein P. Time-course of drug-related psychiatric and behavioral treatment-emergent adverse events during brivaracetam treatment in adults with focal-onset seizures. Epilepsy Behav. 2024 Jul;156:109844. doi: 10.1016/j.yebeh.2024.109844. Epub 2024 May 23.
PubMed 38788664
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00490035
- Acronym / sponsor ID
- N01252
- Conditions
- Epilepsy
- Keywords
- Epilepsy, Brivaracetam, Partial Onset Seizures
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 399 participants (actual)
- Lead sponsor
- UCB Pharma SAIndustry (pharma, biotech, devices)
- Study start
- Sep 2007
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 22 Jun 2007 (estimated)
- Results
- Posted 13 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboMatching Placebo tablets administered twice a day |
| Brivaracetam 20 mg/day | Experimental | Drug: BrivaracetamBrivaracetam 20 mg/day, 10 mg administered twice a day |
| Brivaracetam 50 mg/day | Experimental | Drug: BrivaracetamBrivaracetam 50 mg/day, 25 mg administered twice a day |
| Brivaracetam 100 mg/day | Experimental | Drug: BrivaracetamBrivaracetam 100 mg/day, 50 mg administered twice a day |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboDaily oral dose of two equal intakes, morning and evening, of Placebo in a double-blinded way for the 12-week Treatment Period | Other | Placebo |
| BrivaracetamDaily 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 20 mg/day |
| BrivaracetamDaily 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 50 mg/day |
| BrivaracetamDaily oral dose of two equal intakes, morning and evening, of Brivaracetam 100 mg /day in a double-blinded way for the 12-week Treatment Period. | Drug | Brivaracetam 100 mg/day |
Primary outcome
Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period
Time frame: From Baseline to 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.
22 secondary outcomes
Responder Rate for Partial Onset Seizures (Type I) Frequency Per Week Over the 12-week Treatment Period
Time frame: From Baseline to 12-week Treatment Period
All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period
Time frame: 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
Time frame: 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
Time frame: From Baseline to 12-week Treatment Period
Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period
Time frame: From Baseline to 12-week Treatment Period
Time to First Type I Seizure During the 12-week Treatment Period
Time frame: From Baseline to 12-week Treatment Period
Time to Fifth Type I Seizure During the 12-week Treatment Period
Time frame: From Baseline to 12-week Treatment Period
Time to Tenth Type I Seizure During the 12-week Treatment Period
Time frame: From Baseline to 12-week Treatment Period
Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period.
Time frame: From Baseline to 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score
Time frame: From Baseline to 12-week Treatment Period
Change From Baseline to the 12-week Treatment Period in Hospital Depression Score
Time frame: From Baseline to 12-week Treatment Period
Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit
Time frame: Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit
Time frame: Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
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
Time frame: From Baseline to 12-week Treatment Period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24256083Ryvlin 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.
- Results publication: PubMed 27265725Toledo 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.
- Results publication: PubMed 27335114Ben-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.
- Results publication: PubMed 27589414Brodie 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.
- Results publication: PubMed 28004320Mukuria 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.
- Results publication: PubMed 27608437Moseley 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.
- Results publication: PubMed 28236727Brandt 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.
- Results publication: PubMed 27988967Klein 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.
- Results publication: PubMed 28279891Asadi-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.
- Results publication: PubMed 29414542Benbadis 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.
- Results publication: PubMed 29908435Brodie 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.
- Results publication: PubMed 32432339Klein 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UCB Clinical Trial Call Center study director
+1 877 822 9493 (UCB)
76 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brivaracetam in people with Epilepsy, run by UCB Pharma SA at 76 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 76 sites in Poland, France, Germany, India, Spain and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period (time frame: From Baseline to 12-week Treatment Period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00490035, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2022.