E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015037 |
E.1.2 | Term | Epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of Brivaracetam (BRV) at the doses of 5, 20, and 50 mg/day in b.i.d. administration in reducing seizure frequency in subjects with partial onset seizures not fully controlled despite optimal treatment with one to two concomitant anti-epileptic drug(s) (AED(s)), compared to placebo.
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E.2.2 | Secondary objectives of the trial |
- To confirm the dose/clinical response relationship
- To assess the effects of BRV on Type IC seizures
- To assess the safety and tolerability of BRV
- To assess the effects of BRV on patients’ Health-Related Quality of Life (HRQoL)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subjects were 16 to 70 years, both inclusive. Subjects under 18 years of age were only included where legally permitted and ethically accepted
- Subjects with well-characterized focal epilepsy or epileptic syndrome according to the International League Against Epilepsy (ILAE) classification
- Subjects had a history of partial onset seizures (POS) whether or not secondarily generalized (Type I seizures according to the ILAE classification)
- Subjects had at least 2 POS whether or not secondarily generalized per month during the 3 months preceding Visit 1 (V1)
- Subjects had at least 8 POS whether or not secondarily generalized during the 8-Week Baseline Period
- Subjects were uncontrolled while treated by 1 to 2 permitted concomitant antiepileptic drug(s) (AEDs). Vagal nerve stimulation (VNS) was allowed and was not counted as a concomitant AED
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Partial onset seizure (Type I) frequency per week over the 12-week Treatment Period
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to 12-week Treatment Period
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E.5.2 | Secondary end point(s) |
- Responder rate for partial onset seizures (Type I) frequency per week over the 12-week Treatment Period
- All seizure frequency (Type I+II+III) per week over the 12-week Treatment Period
- Percent change from Baseline to the 12-week Treatment Period in partial onset seizure (Type I) frequency per week
- Categorized percentage change from Baseline in seizure frequency for partial onset seizure (Type I) over the 12-week Treatment Period
- Seizure freedom rate (all seizure types) over the 12-week Treatment Period
- Time to first Type I seizure during the 12-week Treatment Period
- Time to fifth Type I seizure during the 12-week Treatment Period
- Time to tenth Type I seizure during the 12-week Treatment Period
- Reduction of Type IC/Type I seizure frequency ratio from Baseline to the 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
- 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
- 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
- Change from Baseline to the 12-week Treatment Period in remaining QOLIE-31-P domain scores (Energy/Fatigue, Emotional Well-being, Cognitive Functioning, Overall Quality of Life, and Medication effects)
- Change from Baseline to the 12-week Treatment Period in Hospital Anxiety score
- Change from Baseline to the 12-week Treatment Period in Hospital Depression score
- Patient's Global Evaluation Scale (P-GES) evaluated at Last Visit or Early Discontinuation Visit
- Investigator's Global Evaluation Scale (I-GES) evaluated at Last Visit or Early Discontinuation Visit
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Baseline to 12-week Treatment Period
- Baseline to Last Visit or Early Discontinuation Visit in the 12-week Treatment Period
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Australia |
Brazil |
Canada |
Mexico |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |