An international, randomized, double-blind, parallel-group, placebo-controlled, flexible dose study: evaluation of the safety and efficacy of brivaracetam in subjects (>=16 to 70 years old) suffering from localization-related or generalized epilepsy.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-006346-34-BE
• Date of registration: 28/03/2007
• Prospective Registration: Yes
• Primary sponsor: UCB Pharma
• Public title: An international, randomized, double-blind, parallel-group, placebo-controlled, flexible dose study: evaluation of the safety and efficacy of brivaracetam in subjects (>=16 to 70 years old) suffering from localization-related or generalized epilepsy.
• Scientific title: An international, randomized, double-blind, parallel-group, placebo-controlled, flexible dose study: evaluation of the safety and efficacy of brivaracetam in subjects (>=16 to 70 years old) suffering from localization-related or generalized epilepsy.
• Date of first enrolment: 13/06/2007
• Target sample size: 588
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006346-34
• 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

Austria, Belgium, Czech Republic, Germany, Italy, Sweden

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.
• Subjects with well-characterized localization-related epilepsy or generalized epilepsy according to the ILAE classification (1).
• For subjects suffering from:
• localization-related epilepsy (1): subjects having at least 2 partial onset seizures whether or not secondarily generalized per month during the 3 months preceding V1 according to ILAE classification (2).
• generalized epilepsy (1): subjects having at least 2 Type II seizure days per month during the 3 months preceding V1 according to the ILAE classification (2).
• For subjects suffering from:
• localization-related epilepsy (1): subjects having at least 4 partial onset seizures whether or not secondarily generalized during the 4-week Baseline Period
according to the ILAE classification (2).
• generalized epilepsy (1): subjects having at least 4 Type II seizure days during the 4-week Baseline Period according to the ILAE classification (2).
• Subjects being uncontrolled while treated by 1 to 3 permitted concomitant AED(s).
Vagal Nerve Stimulation (VNS) is allowed and will not be counted as a concomitant
AED.
• Permitted concomitant AED(s) and VNS (implanted for at least 9 months) being stable and at optimal dosage for the subject from at least 1 month (3 months for phenobarbital and primidone) before V1 and expected to be kept stable during the Treatment Period. Benzodiazepine (BZD) taken more than once a week (for any indication) will be considered as a concomitant AED.
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:
• Subjects suffering from epilepsies and syndromes undetermined whether focal or
generalized (classification 3 according to the ILAE classification (1)).
• Subjects suffering from special syndromes (classification 4 according to the ILAE
classification (1)).
• For subjects suffering from localization-related epilepsy (1): history or presence of
seizures occurring only in clusters (too frequently or indistinctly separated to be
reliably counted) before V2.
• History or presence of status epilepticus during the year preceding V1 or during
Baseline.
• History or presence of known pseudo-seizures.
• Subjects taking any drug with possible CNS effects except if stable from at least 1
month before V1 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 1 month before V1, and is expected to be kept stable during the Treatment
Period.
• History of cerebrovascular accident (CVA), including transient ischemic attack (TIA),
within the last 6 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

Localization-related or generalized epilepsy
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)

Secondary Objective: •To confirm the efficacy of BRV in reducing partial onset seizure (Type I) frequency in
subjects suffering from localization-related epilepsy.
• To assess the effects of BRV on patients’ Health-Related Quality of Life (HRQoL) in
subjects suffering from localization-related epilepsy.
• To assess the effects of BRV on Type IC seizures.

Exploratory Efficacy Objectives
• To obtain a description of the patient’s self-reported health status.
• To explore direct medical resources use and indirect cost parameters.
• To collect blood samples for genotyping of SV2-and epilepsy-related genes (for a
pooled analysis at the program level).
• To explore the efficacy of BRV in reducing Type II seizure days in subjects suffering
from generalized epilepsy.
• To explore the effects of BRV on patients’ Health-Related Quality of Life (HRQoL) in
subjects suffering from generalized epilepsy.

Primary end point(s): The primary efficacy variable is the partial onset seizure (Type I) frequency per week over the Treatment Period (Dose-finding Period + Maintenance Period) in subjects suffering from localization-related epilepsy.

Safety Variables
• Adverse events reporting.
• Laboratory tests (including blood chemistry, hematology and urinalysis).
• AED and BRV plasma levels.
• Electrocardiogram (ECG).
• Physical and neurological examinations.
• Vital signs including orthostatic measurements.
• Body weight.

Main Objective: To assess the safety and tolerability of BRV at the dose range from 20 to 150 mg/day in b.i.d. administration in subjects suffering from localization-related or generalized epilepsy not fully controlled despite optimal treatment with 1 to 3 concomitant AED(s), compared to placebo (PBO).

Secondary ID(s)

N01254