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. - POS Phase 3

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2006-006344-59-BE
• Date of registration: 14/03/2007
• Prospective Registration: Yes
• Primary sponsor: UCB Pharma S.A.
• Public 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. - POS Phase 3
• Scientific 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. - POS Phase 3
• Date of first enrolment: 07/06/2007
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006344-59
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Finland, France, Germany, Hungary, Italy, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

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 generalizedn(Type I seizures according to the ILAE classification).
• 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).
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Partial Onset Seizures
MedDRA version: 9.1 Level: LLT Classification code 10015037 Term: Epilepsy

Intervention(s)

Product Name: Brivaracetam
Product Code: Brivaracetam
Pharmaceutical Form: Tablet
INN or Proposed INN: Brivaracetam
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-y1] butanamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Brivaracetam
Product Code: Brivaracetam
Pharmaceutical Form: Tablet
INN or Proposed INN: Brivaracetam
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-y1] butanamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Primary Efficacy Variable
The primary efficacy variable is the partial onset seizure (Type I) frequency per week over the Treatment Period.

Secondary Efficacy Variables
• 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 the
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 seizure frequency ratio (Type IC/Type I) from Baseline to the Treatment Period.
• Time to nth (n=1,5,10) Type I seizure during the Treatment Period.

Pharmacokinetic Variables
• BRV (parent compound only) plasma levels.
• Concomitant AED (and/or relevant metabolites) plasma levels.

Safety Variables
• Adverse events reporting.
• Laboratory tests (including blood and urine).
• Electrocardiogram (ECG).
• Vital signs including orthostatic measurements.
• Body weight.

Main Objective: To evaluate the efficacy of brivaracetam (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.

Secondary Objective: - To confirm the dose/clinical response relationship
- To assess the effects of BRV on Type 1C seizures
- To assess the safety and tolerability of BRV
- To assess the effects BRV on patients' Health-Related Quality of Life (HRQoL)
- To obtain a description of the patients' self-reported health status
- To explore direct medical resources use and indirect cost parameters
- To explore the population pharmacokinetics of BRV and identify relevant covariates and to assess the impact of BRV on concomitant AED plasma-levels
- To collect blood samples for genotyping of SV2-and epilepsy-related genes

Secondary ID(s)

N01252