To evaluate the efficacy of BRV at the doses of 20, 50 and 100 mg/day in b.i.d. administration in reducing seizure frequency in subjects with partial onset seizures not fully controlled despite optimal treatment with 1 to 2 concomitant AED(s),…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable is the partial onset seizure (Type I) frequency
per week over the Treatment Period.
Secondary outcome
• Seizure Worry QOLIE-31-P score.
• Daily Activities QOLIE-31-P score.
• Total QOLIE-31-P score.
• Remaining QOLIE-31-P domain scores (Energy/Fatigue, Emotional Well-being,
Mental Activity/Cognitive Functioning, Overall Quality of Life and Medication
effects).
• Hospital Anxiety and Depression Scale (HADS) scores (Anxiety, Depression).
• Patient*s Global Evaluation Scale (GES).
• Investigator*s GES.
• All seizure frequency (Type I + II + III) per week over the Treatment Period.
• Seizure freedom rate (all seizure types).
• Percent reduction for partial onset seizure (Type I) frequency per week from
baseline to the Treatment Period.
• Responder rate (the proportion of subjects who have a >= 50% reduction in
seizure frequency per week from baseline) for partial onset seizures (Type I)
over the Treatment Period.
• Categorized percentage reduction from baseline in seizure frequency for
partial onset seizures (type I) over the Treatment Period. The categories
include: <-25%, -25% to < 25%, 25% to < 50%, 50% to < 75%, 75% to < 100%, and
100%.
• Reduction of Type IC/Type I seizure frequency ratio from baseline to the
Treatment Period.
Background summary
This adequate and well-controlled study will be performed to provide data
confirming the efficacy and safety of brivaracetam (BRV) as an antiepileptic
drug (AED) and to support the marketing authorization application / new drug
application for BRV in the indication of adjunctive treatment in adults (18
years - 70 years) with refractory partial onset seizures (POS) with or without
secondary generalization.
Studies using BRV as adjunctive therapy in POS in adults have shown promising
results in terms of both efficacy (53.05% reduction in seizure frequency per
week from baseline and 55.77% responder rate in Type I seizures) and safety.
The dosages of 20 mg/day, 50 mg/day and 100 mg/day have been chosen based upon
a dose-response analysis performed on the data collected during the phase II
program.
Study objective
To evaluate the efficacy of BRV at the doses of 20, 50 and 100 mg/day in b.i.d.
administration in reducing seizure frequency in subjects with partial onset
seizures not fully controlled despite optimal treatment with 1 to 2 concomitant
AED(s), compared to placebo.
Study design
This is a multicenter, therapeutic confirmatory, parallel-group, double-blind,
randomized, placebo-controlled study with 3 active doses of BRV and possible
conversion to a Long-Term Follow-Up (LTFU) study.
A 1:1:1:1 central randomization (random permuted blocks) stratified for the
study region (Eastern Europe / Western Europe / ROW) and for the use of LEV
(use / no use at study entry) will be used to ensure the balance between the
different treatment groups (PBO, 20 mg BRV, 50 mg BRV and 100 mg BRV).
The number of subjects using LEV as concomitant AED will be limited to 20% of
the total study population.
Intervention
All subjects will be either randomised to brivaracetam:
- 20 mg/day,
- 50 mg/day,
- 100 mg/day or
- matching placebo.
All subjects will be asked to take 3 tablets in the morning and 3 tablets in
the evening.
Study burden and risks
Physical examnination including neurologic examination and mental status 4x
ECG 4x
EEG 1x (unless performed within 5 years before start of study)
MRI/CT scan 1x (unless performed within 2 years before start of study)
3 health questionnaires 4x
lab testing 6x
DNA test 1x
pregnancy test 6x
vital sign's 7x
Chemin du Foriest
B-1420 Braine-l'Alleud
Nederland
Chemin du Foriest
B-1420 Braine-l'Alleud
Nederland
Listed location countries
Age
Inclusion criteria
• Subjects from 16 to 70 years, both inclusive. Subjects under 18 years may only be included where legally permitted and ethically accepted.
• Well-characterized focal epilepsy or epileptic syndrome according to the ILAE classification (1).
• Subjects with a history of partial onset seizures whether or not secondarily generalized (Type I seizures according to the ILAE classification (2)).
• Subjects having at least two partial onset seizures whether or not secondarily generalized per month during the three months preceding Visit 1 (V1).
• Subjects having at least eight partial onset seizures whether or not secondarily generalized during the 8-week Baseline Period.
• Subjects being uncontrolled while treated by one to two permitted concomitant AED(s).
Exclusion criteria
• History or presence of seizures occurring only in clusters (too frequently or indistinctly separated to be reliably counted) before V3.
• History or presence of status epilepticus during the year preceding V1 or during baseline.
• Subject taking any drug with possible relevant CNS effects except if stable from at least 1 month before Visit 1 and expected to be kept stable during the Treatment Period.
• Subjects taking any drug that may significantly influence the metabolism of BRV (CYP2C or CYP3A potent inducers/inhibitors) except if the dose has been kept stable at least one month before V1, and is expected to be kept stable during the Treatment Period.
• History of cerebrovascular accident (CVA), including transient ischemic attack (TIA), in the last six months.
• Presence of any sign (clinical or imaging techniques) suggesting rapidly progressing (i.e. not expected to stay stable during trial participation) brain disorder or brain tumor. Stable arteriovenous malformations, meningiomas or other benign tumors may be acceptable.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-06344-59-NL |
| CCMO | NL17187.068.07 |