A Study to Evaluate the Safety of Brivaracetam to be given by Intravenous Infusion in Subjects Aged Between 16 to 70 years Suffering from Epilepsy

• Register: EUCTR
• Last refreshed on: 24 June 2013
• Main ID: EUCTR2008-004714-27-CZ
• Date of registration: 12/01/2009
• Prospective Registration: Yes
• Primary sponsor: UCB Biosciences, Inc.
• Public title: A Study to Evaluate the Safety of Brivaracetam to be given by Intravenous Infusion in Subjects Aged Between 16 to 70 years Suffering from Epilepsy
• Scientific title: A Multicenter, Open-label, Four-arm, Randomized trial, Evaluating the Safety and Tolerability of Brivaracetam Intravenous Infusion and Bolus, Administered in BID Regimen as an Adjunctive Antiepileptic Treatment in Subjects from 16 to 70 years Suffering from Epilepsy.
• Date of first enrolment: 05/10/2011
• Target sample size: 125
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004714-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: 1 week double blind during the Run in period If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Czech Republic, Germany, 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:
1. An Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved written Informed Consent form signed and dated by the subject or by parent(s) or legal representative(s). The consent form or a specific Assent form, where required, will be signed and dated by minors.
2. Subjects from 16 to 70 years, both inclusive. Subjects under 18 years of age may only be included where legally permitted and ethically accepted. In the Czech Republic and Germany, subjects <18 years of age are not allowed to participate. In the Czech Republic, subjects >65 years of age are not allowed to participate.
3. Subjects with a body weight =40kg.
4. Female subjects without childbearing potential (premenarcheal, postmenopausal for at least 2 years, bilateral oophorectomy, tubal ligation, or 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 (or 50µg ethinylestradiol per intake if associated with carbamazepine [or other strong enzyme inducers eg, phenobarbital, primidone, oxcarbazepine]) must be used in conjunction with a barrier method. Monogamous relationship with partner vasectomized for at least 3 months 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. Sexual inactivity might be accepted on a case-by-case basis based upon Investigator’s judgment.
5. Subject/legal representative considered as 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.
6. Subjects with well-characterized focal or generalized epilepsy or epileptic syndrome according to the ILAE classification.
7. Inpatients and outpatients with a history of POS whether or not secondarily generalized or primary generalized seizures (Type I or II seizures according to the ILAE classification).
8. Subjects being uncontrolled while treated with 1 to 2 permitted concomitant AED(s). Vagal nerve stimulation (VNS) is allowed and will be counted as a concomitant AED.
9. Permitted concomitant AEDs 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 Run-In and Evaluation Periods. Benzodiazepines taken more than once a week (for any indication) will be considered as a concomitant AED.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
1. Mentally impaired subjects unable to understand the study purpose
2. History or presence of status epilepticus during 1 year preceding V1 or during Baseline.
3. Subjects on felbamate with less than 18 months continuous exposure before V1. Subjects having been on felbamate are eligible if the combined duration of treatment and wash-out is =18 months.
4. Subjects currently on vigabatrin. Subjects having been on vigabatrin if no visual fields examination report available including standard static (Humphrey or Octopus) or cinetic perimetry (Goldman) or if results of these examinations are abnormal.
5. 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 Run-in and Evaluation Periods.
6. 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 Run-in and Evaluation Periods.
7. History of cerebrovascular accident (CVA), including transient ischemic attack (TIA), in the last 6 months.
8. Subjects suffering from severe cardiovascular disease or peripheral vascular disease.
9. 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.
10. Any clinical conditions (e.g. bone marrow depression, chronic hepatic disease and/or severe renal impairment) which impair reliable participation in the trial or necessitate the use of medication not allowed by protocol.
11. Presence of a terminal illness.
12. Presence of a serious infection.
13. Subjects with history of severe adverse hematologic reaction to any drug.
14. Subjects suffering from severe disturbance of hemostasis.
15. Subject has impaired liver functions: values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase are more than twice the upper limit of the reference range.
16. Subject having clinically significant deviations from reference range values for laboratory parameters: creatinine clearance calculated < 50 mL/min, platelets < 100,000/µL, or neutrophil cells < 1,800/µL).
17. Clinically significant ECG abnormalities according to the Investigator.
18. Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (“Yes”) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at V1.
19. In the Investigator’s medical judgment, any current suicidal ideation or other serious psychiatric disorders (ie, bipolar disorder, severe depression, psychosis) requiring or having required hospitalization or medication.
20. Known allergic reaction or intolerance to pyrrolidone derivatives and/or investigational product excipients.
21. Known multiple drug allergies or severe drug allergy.
22. Pregnant or lactating women.
23. Known alcohol or drug addiction or abuse within the last two years.
24. Subject institutionalized under judicial decision.
25. Problems of venous accessibility
26. Subject taking part in another clinical/pharmacological trial in the month preceding enrolment (V1).
2

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

Health Condition(s) or Problem(s) studied

Epilepsy
MedDRA version: 14.1 Level: PT Classification code 10015037 Term: Epilepsy System Organ Class: 10029205 - Nervous system disorders

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

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: (2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide
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: (2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide
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: (2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide
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

Product Name: brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BRIVARACETAM
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): Safety Variables
The safety assessment will be made using:
• AEs, with special attention to injection-related AEs (local site and systemic reactions) and seizure worsening
• Seizure counts
• Laboratory tests (hematology, biochemistry, urinalysis, and BRV and AED plasma concentrations)
• ECGs including cardiac telemetry
• Vital signs (including orthostatic measurement), body weight, and height
• Physical and neurological examinations
• Psychiatric and mental status

Main Objective: To evaluate the safety and tolerability of BRV 200mg/day administered intravenously as an infusion or a bolus, according to an initiation or a conversion scheme, during repeated dosing (100mg/administration bid for 4.5 days) as an adjunctive treatment in adult subjects suffering from localization-related or generalized epilepsy

Timepoint(s) of evaluation of this end point: Visit 1 to visit 8

Secondary Objective: • To collect data on health care resource utilization

Secondary Outcome(s)

Secondary end point(s): • Health care resource utilization data (concomitant medications, medical procedures, hospital stays, and health care provider consultations not foreseen by the protocol)

Timepoint(s) of evaluation of this end point: As when occurs

Secondary ID(s)

N01258

Source(s) of Monetary Support

UCB Biosciences, Inc.