Double-blind, Randomized Study Evaluating the Efficacy and Safety of Brivaracetam in Adults With Partial Onset Seizures
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Matching Placebo tablets administered twice a day |
Other: Placebo
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 20 mg/day Brivaracetam 20 mg/day, 10 mg administered twice a day |
Drug: Brivaracetam
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: Brivaracetam 50 mg/day Brivaracetam 50 mg/day, 25 mg administered twice a day |
Drug: Brivaracetam
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.
|
| Experimental: Brivaracetam 100 mg/day Brivaracetam 100 mg/day, 50 mg administered twice a day |
Drug: Brivaracetam
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.
|
Outcome Measures
Primary Outcome Measures
- Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period [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.
Secondary Outcome Measures
- Responder Rate for Partial Onset Seizures (Type I) Frequency Per Week Over the 12-week Treatment Period [From Baseline to 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.
- All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period [From Baseline to 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).
- 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]
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.
- 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]
The categories are: <= 25 % - 25 % to < 25 % 25 % to < 50 % 50 % to < 75 % 75 % to < 100 % 100 %
- Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period [From Baseline to 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.
- Time to First Type I Seizure During the 12-week Treatment Period [From Baseline to 12-week Treatment Period]
The time to first Type I Seizure during the 12-week Treatment Period was measured in days.
- Time to Fifth Type I Seizure During the 12-week Treatment Period [From Baseline to 12-week Treatment Period]
The time to Fifth Type I Seizure during the 12-week Treatment Period was measured in days.
- Time to Tenth Type I Seizure During the 12-week Treatment Period [From Baseline to 12-week Treatment Period]
The time to tenth Type I Seizure during the 12-week Treatment Period was measured in days.
- Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period. [From Baseline to 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.
- 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 [From Baseline to 12-week Treatment Period]
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.
- 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 [From Baseline to 12-week Treatment Period]
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.
- 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 [From Baseline to 12-week Treatment Period]
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.
- Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score [From Baseline to 12-week Treatment Period]
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.
- Change From Baseline to the 12-week Treatment Period in Hospital Depression Score [From Baseline to 12-week Treatment Period]
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.
- Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit [Last Visit or Early Discontinuation Visit in the 12-week Treatment Period]
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?"
- Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit [Last Visit or Early Discontinuation Visit in the 12-week Treatment Period]
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."
- 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 [From Baseline to 12-week Treatment Period]
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.
- 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 [From Baseline to 12-week Treatment Period]
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.
- 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 [From Baseline to 12-week Treatment Period]
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.
- 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 [From Baseline to 12-week Treatment Period]
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.
- 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 [From Baseline to 12-week Treatment Period]
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.
- 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 [From Baseline to 12-week Treatment Period]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 13 | Gent | Belgium | ||
| 2 | 19 | La Louviere | Belgium | ||
| 3 | 12 | Liege | Belgium | ||
| 4 | 10 | Saint-Vith | Belgium | ||
| 5 | 44 | Kuopio | Finland | ||
| 6 | 41 | Oulu | Finland | ||
| 7 | 42 | Seinajoki | Finland | ||
| 8 | 43 | Tampere | Finland | ||
| 9 | 60 | Angers Cedex 9 | France | ||
| 10 | 56 | Bethune | France | ||
| 11 | 62 | Bron | France | ||
| 12 | 57 | Dijon | France | ||
| 13 | 53 | Lille | France | ||
| 14 | 52 | Montpellier Cedex | France | ||
| 15 | 64 | Nancy | France | ||
| 16 | 54 | Paris | France | ||
| 17 | 51 | Rennes | France | ||
| 18 | 61 | Roanne | France | ||
| 19 | 55 | Strasbourg | France | ||
| 20 | 76 | Bad Berka | Germany | ||
| 21 | 73 | Berlin | Germany | ||
| 22 | 79 | Bernau | Germany | ||
| 23 | 78 | Bielefeld | Germany | ||
| 24 | 74 | Freiburg | Germany | ||
| 25 | 75 | Kehl-Kork | Germany | ||
| 26 | 77 | Mainz | Germany | ||
| 27 | 70 | Munchen | Germany | ||
| 28 | 72 | Radeberg | Germany | ||
| 29 | 71 | Ulm | Germany | ||
| 30 | 94 | Budapest | Hungary | ||
| 31 | 90 | Debrecen | Hungary | ||
| 32 | 92 | Pecs | Hungary | ||
| 33 | 256 | Bangalore | India | ||
| 34 | 257 | Bangalore | India | ||
| 35 | 253 | Hyderabad | India | ||
| 36 | 258 | Jaipur | India | ||
| 37 | 255 | Kolkata | India | ||
| 38 | 250 | Lucknow | India | ||
| 39 | 259 | Mumbai | India | ||
| 40 | 251 | Pune Maharashtra | India | ||
| 41 | 270 | Pune | India | ||
| 42 | 104 | Bologna | Italy | ||
| 43 | 105 | Foggia | Italy | ||
| 44 | 101 | Perugia | Italy | ||
| 45 | 103 | Roma | Italy | ||
| 46 | 107 | Roma | Italy | ||
| 47 | 124 | Breda | Netherlands | ||
| 48 | 125 | Den Haag | Netherlands | ||
| 49 | 122 | Zwolle | Netherlands | ||
| 50 | 142 | Bialystok | Poland | ||
| 51 | 143 | Gdansk | Poland | ||
| 52 | 153 | Grodzisk Mazowiecki | Poland | ||
| 53 | 147 | Katowice | Poland | ||
| 54 | 151 | Katowice | Poland | ||
| 55 | 141 | Kielce | Poland | ||
| 56 | 150 | Krakow | Poland | ||
| 57 | 148 | Lodz | Poland | ||
| 58 | 144 | Lublin | Poland | ||
| 59 | 152 | Poznan | Poland | ||
| 60 | 146 | Szczecin | Poland | ||
| 61 | 145 | Warsaw | Poland | ||
| 62 | 140 | Warszawa | Poland | ||
| 63 | 149 | Warszawa | Poland | ||
| 64 | 187 | Alcorcon | Spain | ||
| 65 | 181 | Barcelona | Spain | ||
| 66 | 182 | Madrid | Spain | ||
| 67 | 184 | San Sebastian | Spain | ||
| 68 | 183 | Vigo | Spain | ||
| 69 | 185 | Zaragoza | Spain | ||
| 70 | 201 | Biel | Switzerland | ||
| 71 | 205 | Geneve | Switzerland | ||
| 72 | 203 | St Gallen | Switzerland | ||
| 73 | 202 | Tschugg | Switzerland | ||
| 74 | 204 | Zürich | Switzerland | ||
| 75 | 223 | Liverpool | United Kingdom | ||
| 76 | 224 | Middlesborough | United Kingdom |
Sponsors and Collaborators
- UCB Pharma SA
Investigators
- Study Director: UCB Clinical Trial Call Center, +1 877 822 9493 (UCB)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- N01252
- 2006-006344-59
Study Results
Participant Flow
| Recruitment Details | This study started to enroll subjects in September 2007 and concluded in February 2009. |
|---|---|
| Pre-assignment Detail | Participant Flow refers to the Randomized Set. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Period Title: Overall Study | ||||
| STARTED | 100 | 99 | 100 | 100 |
| COMPLETED | 92 | 93 | 88 | 94 |
| NOT COMPLETED | 8 | 6 | 12 | 6 |
Baseline Characteristics
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day | Total Title |
|---|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day | |
| Overall Participants | 100 | 99 | 100 | 100 | 399 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
36.4
(13.0)
|
35.7
(12.5)
|
39.0
(13.5)
|
38.0
(13.1)
|
37.24
(13.05)
|
| Age, Customized (participants) [Number] | |||||
| <18 years |
2
2%
|
2
2%
|
0
0%
|
1
1%
|
5
1.3%
|
| Between 18 and 65 years |
96
96%
|
94
94.9%
|
97
97%
|
96
96%
|
383
96%
|
| >=65 years |
2
2%
|
3
3%
|
3
3%
|
3
3%
|
11
2.8%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
46
46%
|
38
38.4%
|
45
45%
|
42
42%
|
171
42.9%
|
| Male |
54
54%
|
61
61.6%
|
55
55%
|
58
58%
|
228
57.1%
|
| Region of Enrollment (Number) [Number] | |||||
| Hungary |
4
4%
|
2
2%
|
3
3%
|
3
3%
|
12
3%
|
| Poland |
26
26%
|
28
28.3%
|
27
27%
|
27
27%
|
108
27.1%
|
| India |
23
23%
|
22
22.2%
|
23
23%
|
23
23%
|
91
22.8%
|
| Belgium |
3
3%
|
0
0%
|
3
3%
|
0
0%
|
6
1.5%
|
| Finland |
3
3%
|
3
3%
|
1
1%
|
4
4%
|
11
2.8%
|
| France |
17
17%
|
17
17.2%
|
11
11%
|
15
15%
|
60
15%
|
| Germany |
8
8%
|
10
10.1%
|
14
14%
|
9
9%
|
41
10.3%
|
| Italy |
4
4%
|
8
8.1%
|
3
3%
|
5
5%
|
20
5%
|
| Netherlands |
3
3%
|
0
0%
|
1
1%
|
3
3%
|
7
1.8%
|
| Spain |
8
8%
|
4
4%
|
6
6%
|
4
4%
|
22
5.5%
|
| Switzerland |
1
1%
|
3
3%
|
6
6%
|
5
5%
|
15
3.8%
|
| United Kingdom |
0
0%
|
2
2%
|
2
2%
|
2
2%
|
6
1.5%
|
Outcome Measures
| Title | Partial Onset Seizure (Type I) Frequency Per Week Over the 12-week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| Median (Inter-Quartile Range) [Seizure Frequency per Week] |
1.75
|
1.34
|
1.49
|
1.26
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Brivaracetam 50 mg/Day |
|---|---|---|
| Comments | In order to control the Type I error testing was performed in sequence starting with 50 mg, then 100 mg and finally 20 mg Brivaracetam per day versus Placebo, only moving to the next test if the previous one was significant at the 5 % level. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.261 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage Reduction over Placebo |
| Estimated Value | 6.5 | |
| Confidence Interval |
(2-Sided) 95% -5.2 to 16.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Responder Rate for Partial Onset Seizures (Type I) Frequency Per Week Over the 12-week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| Non-responders |
80.0
80%
|
72.7
73.4%
|
72.7
72.7%
|
64.0
64%
|
| Responders |
20.0
20%
|
27.3
27.6%
|
27.3
27.3%
|
36.0
36%
|
| Title | All Seizure Frequency (Type I+II+III) Per Week Over the 12-week Treatment Period |
|---|---|
| Description | There are three types of Epilepsy: Partial Epilepsies (Type I), Generalized Epilepsies (Type II) and uncertain classification of Epilepsies (Type III). |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| Median (Inter-Quartile Range) [Times per week] |
1.75
|
1.34
|
1.49
|
1.26
|
| Title | Percent Change From Baseline to the 12-week Treatment Period in Partial Onset Seizure (Type I) Frequency Per Week |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| Median (Inter-Quartile Range) [Percent change in seizures per week] |
-17.03
|
-30.03
|
-26.83
|
-32.45
|
| Title | Categorized Percentage Change From Baseline in Seizure Frequency for Partial Onset Seizure (Type I) Over the 12-week Treatment Period |
|---|---|
| Description | The categories are: <= 25 % - 25 % to < 25 % 25 % to < 50 % 50 % to < 75 % 75 % to < 100 % 100 % |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| <= 25 % |
19.0
19%
|
10.1
10.2%
|
15.2
15.2%
|
10.0
10%
|
| - 25 % to < 25 % |
41.0
41%
|
35.4
35.8%
|
33.3
33.3%
|
33.0
33%
|
| 25 % to < 50 % |
20.0
20%
|
27.3
27.6%
|
24.2
24.2%
|
21.0
21%
|
| 50 % to < 75 % |
12.0
12%
|
18.2
18.4%
|
17.2
17.2%
|
14.0
14%
|
| 75 % to < 100 % |
8.0
8%
|
7.1
7.2%
|
9.1
9.1%
|
18.0
18%
|
| 100 % |
0
0%
|
2.0
2%
|
1.0
1%
|
4.0
4%
|
| Title | Seizure Freedom Rate (All Seizure Types) Over the 12-week Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| Seizure free |
0
0%
|
2.0
2%
|
0
0%
|
4.0
4%
|
| No Seizures but non-completer |
0
0%
|
0
0%
|
1.0
1%
|
0
0%
|
| Not Seizure-free |
100.0
100%
|
98.0
99%
|
99.0
99%
|
96.0
96%
|
| Title | Time to First Type I Seizure During the 12-week Treatment Period |
|---|---|
| Description | The time to first Type I Seizure during the 12-week Treatment Period was measured in days. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| Median (95% Confidence Interval) [Days] |
4
|
6
|
6
|
4
|
| Title | Time to Fifth Type I Seizure During the 12-week Treatment Period |
|---|---|
| Description | The time to Fifth Type I Seizure during the 12-week Treatment Period was measured in days. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| Median (95% Confidence Interval) [Days] |
19
|
25
|
24
|
24
|
| Title | Time to Tenth Type I Seizure During the 12-week Treatment Period |
|---|---|
| Description | The time to tenth Type I Seizure during the 12-week Treatment Period was measured in days. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 100 | 99 | 99 | 100 |
| Median (95% Confidence Interval) [Days] |
39
|
49
|
40
|
46
|
| Title | Reduction of Type IC/Type I Seizure Frequency Ratio From Baseline to the 12- Week Treatment Period. |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) population was defined as all randomized subjects who received at least 1 dose of study medication. Type IC Population consists of those subjects with at least one Type IC seizure during the Baseline period. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 37 | 36 | 40 | 39 |
| Number [percentage of participants] |
45.9
45.9%
|
47.2
47.7%
|
62.5
62.5%
|
41.0
41%
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-To-Treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 86 | 91 | 94 | 80 |
| Mean (Standard Deviation) [units on a scale] |
2.29
(14.03)
|
4.50
(12.71)
|
3.09
(14.43)
|
1.78
(13.95)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-To-Treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 88 | 93 | 96 | 86 |
| Mean (Standard Deviation) [units on a scale] |
8.25
(22.01)
|
6.23
(17.97)
|
5.34
(23.81)
|
8.04
(26.26)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 88 | 93 | 96 | 85 |
| Mean (Standard Deviation) [units on a scale] |
-2.09
(20.26)
|
3.35
(19.72)
|
3.09
(20.79)
|
3.50
(22.52)
|
| Title | Change From Baseline to the 12-week Treatment Period in Hospital Anxiety Score |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 86 | 91 | 95 | 83 |
| Mean (Standard Deviation) [units on a scale] |
-1.54
(3.89)
|
-0.59
(3.89)
|
-0.41
(3.82)
|
0.08
(3.60)
|
| Title | Change From Baseline to the 12-week Treatment Period in Hospital Depression Score |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit / Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 86 | 91 | 95 | 83 |
| Mean (Standard Deviation) [units on a scale] |
-0.65
(3.58)
|
-0.10
(3.67)
|
0.26
(3.84)
|
-0.24
(3.69)
|
| Title | Patient's Global Evaluation Scale (P-GES) Evaluated at Last Visit or Early Discontinuation Visit |
|---|---|
| Description | 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?" |
| Time Frame | Last Visit or Early Discontinuation Visit in the 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 81 | 90 | 90 | 85 |
| Mean (Standard Deviation) [units on a scale] |
4.93
(1.39)
|
5.17
(1.27)
|
5.04
(1.29)
|
5.47
(1.16)
|
| Title | Investigator's Global Evaluation Scale (I-GES) Evaluated at Last Visit or Early Discontinuation Visit |
|---|---|
| Description | 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." |
| Time Frame | Last Visit or Early Discontinuation Visit in the 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 96 | 99 | 98 | 100 |
| Mean (Standard Deviation) [units on a scale] |
4.78
(1.20)
|
4.99
(1.15)
|
4.99
(1.10)
|
5.34
(1.12)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 86 | 92 | 95 | 83 |
| Mean (Standard Deviation) [units on a scale] |
3.49
(19.22)
|
3.53
(17.04)
|
1.95
(20.74)
|
1.99
(20.42)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 88 | 93 | 96 | 84 |
| Mean (Standard Deviation) [units on a scale] |
3.80
(18.71)
|
3.75
(15.94)
|
3.13
(19.35)
|
-2.45
(18.55)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 88 | 93 | 96 | 85 |
| Mean (Standard Deviation) [units on a scale] |
1.80
(19.16)
|
5.36
(20.69)
|
1.02
(19.95)
|
0.69
(16.66)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 88 | 92 | 96 | 86 |
| Mean (Standard Deviation) [units on a scale] |
0.92
(28.93)
|
3.64
(29.24)
|
-0.85
(24.36)
|
3.00
(28.22)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 88 | 93 | 95 | 86 |
| Mean (Standard Deviation) [units on a scale] |
5.11
(18.48)
|
4.52
(16.73)
|
4.55
(18.93)
|
2.24
(18.45)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to 12-week Treatment Period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the Intention-to-treat (ITT) population with measurements at Baseline and Last Visit or Early Discontinuation Visit. |
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day |
| Measure Participants | 88 | 93 | 95 | 84 |
| Mean (Standard Deviation) [units on a scale] |
6.6
(16.3)
|
6.9
(20.1)
|
9.7
(19.8)
|
4.9
(18.1)
|
Adverse Events
| Time Frame | Adverse Events (AEs) were collected up to 23 weeks from Visit 1 (Week -8) to the Safety Visit (Week 15). | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse Events (AEs) refer to the Safety Set (SS) population wich contains the same set of subjects as the Intention-To-Treat (ITT) population. | |||||||
| Arm/Group Title | Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day | ||||
| Arm/Group Description | Matching Placebo tablets administered twice a day | Brivaracetam 20 mg/day, 10 mg administered twice a day | Brivaracetam 50 mg/day, 25 mg administered twice a day | Brivaracetam 100 mg/day, 50 mg administered twice a day | ||||
All Cause Mortality |
||||||||
| Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/100 (6%) | 2/99 (2%) | 4/99 (4%) | 2/100 (2%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 1/100 (1%) | 1 | 0/99 (0%) | 0 | 0/99 (0%) | 0 | 0/100 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Gastritis erosive | 0/100 (0%) | 0 | 0/99 (0%) | 0 | 1/99 (1%) | 1 | 0/100 (0%) | 0 |
| Infections and infestations | ||||||||
| Sepsis | 1/100 (1%) | 1 | 0/99 (0%) | 0 | 0/99 (0%) | 0 | 0/100 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Humerus fracture | 0/100 (0%) | 0 | 0/99 (0%) | 0 | 0/99 (0%) | 0 | 1/100 (1%) | 1 |
| Jaw fracture | 0/100 (0%) | 0 | 1/99 (1%) | 1 | 0/99 (0%) | 0 | 0/100 (0%) | 0 |
| Nervous system disorders | ||||||||
| Convulsion | 3/100 (3%) | 4 | 0/99 (0%) | 0 | 1/99 (1%) | 1 | 0/100 (0%) | 0 |
| Grand mal convulsion | 0/100 (0%) | 0 | 0/99 (0%) | 0 | 1/99 (1%) | 1 | 0/100 (0%) | 0 |
| Status epilepticus | 0/100 (0%) | 0 | 0/99 (0%) | 0 | 0/99 (0%) | 0 | 1/100 (1%) | 1 |
| Pregnancy, puerperium and perinatal conditions | ||||||||
| Abortion spontaneous | 0/100 (0%) | 0 | 1/99 (1%) | 1 | 0/99 (0%) | 0 | 0/100 (0%) | 0 |
| Pregnancy | 1/100 (1%) | 1 | 0/99 (0%) | 0 | 0/99 (0%) | 0 | 0/100 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Amnesia | 0/100 (0%) | 0 | 0/99 (0%) | 0 | 1/99 (1%) | 1 | 0/100 (0%) | 0 |
| Psychotic Disorder | 0/100 (0%) | 0 | 0/99 (0%) | 0 | 1/99 (1%) | 1 | 0/100 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Vaginal hemorrhage | 0/100 (0%) | 0 | 1/99 (1%) | 1 | 0/99 (0%) | 0 | 0/100 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | Brivaracetam 20 mg/Day | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/100 (22%) | 31/99 (31.3%) | 35/99 (35.4%) | 37/100 (37%) | ||||
| Ear and labyrinth disorders | ||||||||
| Vertigo | 3/100 (3%) | 5 | 1/99 (1%) | 2 | 2/99 (2%) | 2 | 8/100 (8%) | 26 |
| Gastrointestinal disorders | ||||||||
| Nausea | 4/100 (4%) | 4 | 0/99 (0%) | 0 | 1/99 (1%) | 1 | 6/100 (6%) | 7 |
| General disorders | ||||||||
| Fatigue | 2/100 (2%) | 2 | 3/99 (3%) | 4 | 4/99 (4%) | 5 | 8/100 (8%) | 9 |
| Infections and infestations | ||||||||
| Nasopharyngitis | 1/100 (1%) | 1 | 8/99 (8.1%) | 8 | 1/99 (1%) | 1 | 2/100 (2%) | 2 |
| Nervous system disorders | ||||||||
| Convulsion | 1/100 (1%) | 1 | 5/99 (5.1%) | 7 | 1/99 (1%) | 1 | 2/100 (2%) | 2 |
| Dizziness | 5/100 (5%) | 11 | 5/99 (5.1%) | 8 | 7/99 (7.1%) | 12 | 5/100 (5%) | 5 |
| Headache | 10/100 (10%) | 14 | 14/99 (14.1%) | 19 | 18/99 (18.2%) | 31 | 9/100 (9%) | 15 |
| Somnolence | 6/100 (6%) | 6 | 8/99 (8.1%) | 10 | 6/99 (6.1%) | 7 | 8/100 (8%) | 8 |
| Psychiatric disorders | ||||||||
| Irritability | 0/100 (0%) | 0 | 0/99 (0%) | 0 | 5/99 (5.1%) | 5 | 1/100 (1%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | UCB Clinical Trial Call Center |
|---|---|
| Organization | UCB |
| Phone | +1 877 822 9493 |
- N01252
- 2006-006344-59