A blind (not knowing which treatment to receive), placebo-controlled (with chance to receive sugar pill) study to evaluate whether Brivaracetam can be used treating partial onset seizures in patients with epilepsy (= 16 to 80 years old)

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2010-019361-28-BE
• Date of registration: 20/10/2010
• Prospective Registration: Yes
• Primary sponsor: UCB BioSciences Inc. A Member of the UCB Group of Companies
• Public title: A blind (not knowing which treatment to receive), placebo-controlled (with chance to receive sugar pill) study to evaluate whether Brivaracetam can be used treating partial onset seizures in patients with epilepsy (= 16 to 80 years old)
• Scientific title: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF BRIVARACETAM IN SUBJECTS (=16 TO 80 YEARS OLD) WITH PARTIAL ONSET SEIZURES
• Date of first enrolment: 15/03/2011
• Target sample size: 900
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019361-28
• 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 Number of treatment arms in the trial: 3

Countries of recruitment

Austria, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Estonia, Finland, Germany, Hong Kong, Hungary, India, Italy, Korea, Republic of, Latvia, Lithuania, Mexico, Netherlands, Romania, Russian Federation, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Clin Trial Reg & Results Disclosure
• Affiliation: UCB Biosciences GmBH

• Name: Clin Trial Reg & Results Disclosure
• Affiliation: UCB Biosciences GmBH

Key inclusion & exclusion criteria

Inclusion criteria:
• An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form is signed and dated by the subject or by the parent(s) or legal representative. The consent form or a specific assent form, where required, will be signed and dated by minors.
• Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, or medication intake according to the judgment of the Investigator.
• Subjects (male or female) from 16 to 80 years, both inclusive. Subjects under 18 years may only be included where legally permitted and ethically accepted.
• Subjects with a body weight =40kg.
• Female subjects without childbearing potential (premenarcheal, postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method. Oral or depot contraceptive treatment with at least 30µg ethinylestradiol per intake [or 50µg ethinylestradiol per intake if associated with any strong enzyme inducer (eg carbamazepine, phenobarbital, primidone, phenytoin, oxcarbazepine, St. John’s Wort, rifampicin)], monogamous relationship with vasectomized partner, or double-barrier contraception are acceptable methods. The subject must understand the consequences and potential risks of inadequately protected sexual activity, be educated about and understand the proper use of contraceptive methods, and undertake to inform the Investigator of any potential change in status. Abstinence will be considered as an acceptable method of contraception if the Investigator can document that the subject agrees to be compliant.
• Well-characterized focal epilepsy/epileptic syndrome according to the 1989 International League Against Epilepsy (ILAE) classification.
• Presence of an EEG reading compatible with the clinical diagnosis of focal epilepsy within the last 5 years.
• Presence of a brain MRI/computed tomography (CT) scan performed within the last 2 years.
• Subjects having at least 8 Type I seizures [POS; focal seizures (according to the 1981 ILAE classification)] during the 8-week Baseline Period with at least 2 Type I seizures during each 4-week interval of the Baseline Period.
• Subjects having at least 2 partial onset seizures whether or not secondarily generalized per month during the 3 months preceding V1.
• Subjects being uncontrolled while treated by 1 or 2 permitted concomitant AED(s). Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED.
• Permitted concomitant AED(s) and VNS being stable and at optimal dosage for the subject from at least 1 month (3 months for phenobarbital, phenytoin, and primidone) before V1 and expected to be kept stable during the Baseline and Treatment Period. Benzodiazepine 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: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
• Subject previously randomized within this study or any other prior study with BRV.
• Seizure type IA (1981 ILAE classification) nonmotor as only seizure type.
• Subject has participated in another study of an investigational medication or a medical device within the last 30 days or is currently participating in another study of an investigational medication or a medical device.
• Subject is currently treated with LEV.
• Subject has taken LEV within 90 days prior to V1.
• Subject has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject’s ability to participate in this study.
• Subject has a known hypersensitivity to any components of the investigational medicinal product or comparative drugs as stated in this protocol.
• Subject not able to read and understand the informed consent form, assent form, or seizure diary card instructions.
• Subject has obvious cognitive impairment or mental retardation as per Investigator assessment.
• Subjects whose seizures could not be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries).
• Subject has history or presence of status epilepticus during the year preceding V1 or during Baseline.
• Subject has history or presence of known psychogenic nonepileptic seizures.
• Subject on felbamate with less than 18 months exposure before V1.
• Subject currently on vigabatrin. Subject with history of vigabatrin use but either no visual fields examination report available including standard static (Humphrey or Octopus) or kinetic perimetry (Goldman) or results of these examinations are abnormal.
• Subject taking any drug with possible central nervous system (CNS) effects except if stable from at least 1 month before V1 and expected to be kept stable during the Treatment Period.
• Subject taking any drug that may significantly influence the metabolism of BRV cytochrome P450 (potent inducers) 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.
• Subject has history of cerebrovascular accident, including transient ischemic attack in the last 6 months.
• Subject is suffering from severe cardiovascular disease or peripheral vascular disease
• Subject has presence of any sign (clinical or imaging techniques) suggesting rapidly progressing (ie not expected to stay stable during study participation) brain disorder or brain tumor. Stable arteriovenous malformations, meningiomas, or other benign tumors may be acceptable.
• Subject has any clinical conditions (eg, bone marrow depression, chronic hepatic disease, and/or severe renal impairment) which impair reliable participation in the study or necessitate the use of medication not allowed by protocol.
• Subject has presence of a terminal illness.
• Subject has presence of a serious infection.
• Subject has history of severe adverse hematologic reaction to any drug.
• Subject is suffering from severe disturbance of hemostasis.
• Subject has impaired hepatic function:ALT/SGPT (alanine aminotransferase/serum glutamic pyruvate transaminase), AST/SGOT (aspartate aminotransferase/serum glutamic oxaloacetic transaminase), alkaline phosphatase of more than 2 times the upper limit of the reference range.
• Gamma-glutamyltransferase (GGT) values of more than 3 times the upper limit of the reference range. A result of GGT exceeding 3 times the upper limit ca

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Focal Epilepsy
MedDRA version: 14.1 Level: PT Classification code 10061334 Term: Partial seizures System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: brivaracetam
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (a1S, 4R)-a-ethyl-2-oxo-4-propyl- 1-pyrrolidineacetamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: brivaracetam
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (a1S, 4R)-a-ethyl-2-oxo-4-propyl- 1-pyrrolidineacetamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: brivaracetam
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (a1S, 4R)-a-ethyl-2-oxo-4-propyl- 1-pyrrolidineacetamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Partial onset seizure (POS) (Type I seizures ) frequency over the Treatment Period standardized to a 28-day duration. The primary efficacy outcome for USA will be percent reduction in POS frequency over placebo based on analysis of covariance. The primary outcome for European authorities will be the 50% responder rate based on percent reduction in weekly POS frequency from Baseline to the Treatment Period.

Secondary Objective: To assess the safety and tolerability of BRV.

Main Objective: To evaluate the efficacy of BRV at doses of 100 and 200mg/day compared to PBO as adjunctive treatment in adult focal epilepsy subjects with partial onset seizures not fully controlled despite current treatment with 1 or 2 concomitant AEDs.

Timepoint(s) of evaluation of this end point: Baseline to 12-week Treatment Period

Secondary Outcome(s)

Secondary end point(s): To assess the safety and tolerability of BRV. Safety variables are AEs,
laboratory tests (blood chemistry, hematology, urinalysis, and
pregnancy test), ECG, vital signs, body weight, physical examination,
neurological examination, mental status, and psychiatric status.

Timepoint(s) of evaluation of this end point: From Baseline to week 18

Secondary ID(s)

N01358

NCT01261325

Source(s) of Monetary Support

UCB BIOSCIENCES, INC. A Member of the UCB Group of Companies