An Open-Label Trial to look at the long-term safety and effectiveness of Brivaracetam used in addition to the subjects main treatment in subjects aged 16 years or older with epilepsy

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2012-000827-42-GB
• Date of registration: 02/05/2012
• Prospective Registration: Yes
• Primary sponsor: UCB Pharma SA
• Public title: An Open-Label Trial to look at the long-term safety and effectiveness of Brivaracetam used in addition to the subjects main treatment in subjects aged 16 years or older with epilepsy
• Scientific title: AN OPEN-LABEL, MULTICENTER, FOLLOW-UP STUDY TO EVALUATE THE LONG-TERM SAFETY AND EFFICACY OF BRIVARACETAM USED AS ADJUNCTIVE TREATMENT IN SUBJECTS AGED 16 YEARS OR OLDER WITH EPILEPSY
• Date of first enrolment: 27/09/2012
• Target sample size: 650
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000827-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Spain, 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:
1. An Independent Ethics Committee (IEC)/Institutional Review Board (IRB) approved written Informed Consent form is signed and dated by the subject or by the parent(s) or legal representative. The Informed Consent form or a specific Assent form, where required, will be signed and dated by minors.
2. Subject is male or female and 16 years or older. Subjects under 18 years of age may be included only where legally permitted and ethically accepted.
3. Subjects having completed the Treatment Period of N01394, N01395, or other planned BRV Phase 3b studies in epilepsy, and have access to the present study.
4. Subject for whom the Investigator believes a reasonable benefit from the long-term administration of BRV may be expected.
5. Female subject without childbearing potential (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 ethinylestradiol 30µg per intake (or ethinylestradiol 50µg 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. True abstinence when this is in line with the preferred and usual lifestyle of the subject will be
considered as an acceptable method of contraception if the Investigator can document that the subject agrees to be compliant (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
6. Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries and questionnaires), visit schedule, or medication intake according to the judgment of the Investigator.

Are the trial subjects under 18? yes
Number of subjects for this age range: 13
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 624
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion criteria:
1. Subject has developed hypersensitivity to any components of the investigational medicinal product (IMP) or comparative drugs as stated in this protocol during the course of the prior study.
2. Severe medical, neurological, or psychiatric disorders, or laboratory values that may have an impact on the safety of the subject.
3. Poor compliance with the visit schedule or medication intake in the previous BRV study.
4. Planned participation in any other clinical study of another investigational drug or device during this study.
5. Pregnant or lactating woman.
6. Any medical condition which, in the Investigator’s opinion, warrants exclusion.
7. Subject has a lifetime history of suicide attempt (including an actual 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 the last visit of the previous study or at the EV of N01372 if not completed at the last visit of the previous study.
8. Subject has impaired hepatic function: ALT/SGPT (alanine aminotransferase/serum glutamic pyruvate transaminase), AST/SGOT (aspartate aminotransferase/serum glutamic
oxaloacetic transaminase), or alkaline phosphatase of more than 2 times the upper limit of the reference range.
9. Subject has 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 can be
accepted only if attributable to hepatic enzyme induction caused by concomitant antiepileptic treatment and other hepatic enzymes are below 2 times the upper limit of the reference range.
10. Subject has clinically significant deviations from reference range values for laboratory parameters: creatinine clearance (CrCl) calculated <30mL/min, platelets <100,000/µL, or neutrophil cells <1,800/µL.


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

Health Condition(s) or Problem(s) studied

Nonpyschotic Behavioural Side Effects in Subjects With 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
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BRIVARACETAM
CAS Number: 357336-20-0
Current Sponsor code: ucb34714
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-

Product Name: Brivaracetam
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BRIVARACETAM
CAS Number: 357336-20-0
Current Sponsor code: ucb34714
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-

Product Name: Brivaracetam
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BRIVARACETAM
CAS Number: 357336-20-0
Current Sponsor code: ucb34714
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-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 'Occurrence of a TEAE', ‘Withdrawal due to an AE’ and ‘Occurrence of an SAE’ ongoing on a daily basis. Laboratory tests (hematology, blood chemistry, urinalysis), and Vital signs (systolic blood pressure, diastolic blood pressure, pulse rate) every 3 months; and body weight, ECG, and Physical and neurological examinations every 6 months.

Primary end point(s): The primary objective is to evaluate the long-term safety and tolerability of BRV at individualized doses up to a maximum of 200mg/day as adjunctive treatment in adult subjects with epilepsy.

Main Objective: To evaluate the long-term safety and tolerability of BRV at individualized doses up to a maximum of 200mg/day as adjunctive treatment in adult subjects with epilepsy

Secondary Objective: To evaluate the maintenance of efficacy of BRV over time.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Ongoing on a daily basis

Secondary end point(s): Evaluate the maintenance of efficacy of BRV over time by means of seizure count information recorded on the Daily Record Card. Secondary efficacy variables for subjects with focal-onset epilepsy are the partial-onset seizure (POS) (Type I) frequency per 28 days during the Evaluation Period, the percent reduction in POS (Type I) frequency per 28 days from Baseline of the previous study to the Evaluation Period, and the responder rate in POS (Type I) frequency over the Evaluation Period. A responder is defined as a subject with a =50% reduction in seizure frequency from the Baseline Period of the previous study. No secondary efficacy variables are defined for subjects with generalized epilepsy.
Other efficacy variables for subjects with focal-onset epilepsy include the percentage of subjects continuously seizure free for all seizure types (I+II+III) for at least 6 months and at least 12 months during the Evaluation Period.
Other efficacy variables for subjects with generalized epilepsy include the number of generalized (Type II) seizure days per 28 days during the Evaluation Period, the percent reduction in generalized (Type II) seizure days per 28 days from Baseline of the previous study to the Evaluation Period, the responder rate for generalized (Type II) seizure days over the Evaluation Period, and the percentage of subjects continuously seizure free for all seizure types (I+II+III) for at least 6 months and at least 12 months during the Evaluation Period.

Secondary ID(s)

N01372

Source(s) of Monetary Support

UCB Pharma SA

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 26/07/2017
• Date Completed: 09/08/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-000827-42/results