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
Conditions
Sponsors
UCB Pharma SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 Informed Consent form or a specific Assent form, where required, will be signed and dated by minors. 2. 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. 3. 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. 4. Subject has a family member/caregiver or close contact person who is knowledgeable on a daily basis regarding the subject’s side effects. This family member/caregiver or close contact person should accompany the subject to the study visits or be available for discussion by telephone. 5. Subject with well-characterized epilepsy according to the 1989 ILAE classification. 6. Subject with epilepsy who the Investigator expects would have benefitted or is benefitting from LEV but for whom the Investigator has decided to discontinue LEV due to nonpsychotic behavioral side effects following the introduction of LEV. 7. Subject is currently receiving LEV at the recommended therapeutic dose (dose ranging from 1g/day and 3g/day) for up to 16 weeks prior to V1. 8. Subject currently treated with 2 to 3 AEDs, including LEV. Vagal nerve stimulation (VNS) is allowed provided it has been implanted for at least 9 months prior to V1. VNS will be counted as a concomitant AED. 9. Permitted concomitant AED(s) (with the exception of LEV) and VNS are stable and at optimal dosage for the subject from at least 4 weeks (12 weeks for phenobarbital, phenytoin, and primidone) before V1 and are expected to be kept stable during the Screening and Treatment Periods. 10. Subject with a body weight =40kg. 11. Female subjects 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. 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, postovulation methods] and withdrawal are not acceptable methods of contra
Exclusion criteria
Exclusion criteria: 1. Subject has previously participated in this study or subject has previously been assigned to treatment in a study of the medication under investigation in this study. 2. 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). 3. Subject has a history of chronic alcohol or drug abuse within the last year. 4. 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. 5. Subject has a lifetime history of suicide attempt (including an actual, interrupted or aborted attempt), or has had 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. 6. Subject has a known hypersensitivity to any components of the investigational medicinal product (IMP) or comparative drugs as stated in this protocol. 7. Subject has history of severe adverse hematologic reaction to any drug. 8. Subject has been receiving LEV at the recommended therapeutic dose (dose ranging from 1g/day to 3g/ day for more than 16 weeks prior to V1. 9. Subject taking any drug that may significantly influence the metabolism of BRV, such as 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. 10. Subject on felbamate with less than 18 months exposure before V1. 11. Subject not able to understand the Informed Consent form, Assent form, or daily record card (DRC) instructions. 12. Subject has obvious cognitive impairment or mental retardation as per Investigator assessment. 13. Subject whose seizures cannot be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries). 14. Subject has history or presence of status epilepticus during the year preceding V1 or during the Screening Period. 15. Subject has history or presence of known psychogenic nonepileptic seizures. 16. 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. 17. Subject has any clinical conditions (eg, bone marrow depression, chronic hepatic disease,a nd/or severe renal impairment) that impair reliable participation in the study or necessitate the use of medication not allowed by protocol. 18. Subject is suffering from severe cardiovascular disease or peripheral vascular disease. 19. Subject has presence of a terminal illness. 20. Subject has presence of a serious infection. 21. Subject has impaired hepatic function: ALT/SGPT (alanine aminotransferase/serum glutamic pyruvate transaminase), AST/SGOT (aspartate aminotransferase/serum glutamic oxaloacetic transami
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1) Between V2 (Week 0) and Visit 6 (Week 12) 2) Between V2 (Week 0) and Visit 6 (Week 12) ;Main Objective: To evaluate the reduction of nonpsychotic behavioral side effects in subjects with epilepsy who switched to BRV 200mg/day after discontinuing LEV 1g/day to 3g/day due to these nonpsychotic behavioral side effects; Secondary Objective: • To evaluate the reduction in intensity of nonpsychotic behavioral side effects in subjects with epilepsy who switched to BRV 200mg/day after discontinuing LEV use due to these nonpsychotic behavioral side effects • To evaluate the efficacy of BRV compared to a retrospective Baseline • To assess the overall safety and tolerability of BRV 200mg/day as adjunctive treatment in adult subjects with epilepsy after they have switched from LEV to BRV treatment ; Primary end point(s): 1)Percentage of subjects who have achieved a clinically meaningful reduction of nonpsychotic behavioral side effects from study entry to the end of the Treatment Period, based on the Investigator’s overall assessment. 2) Entry into the Long-Term Follow Up extension study (N01372) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The safety and efficacy variables be assessed as specified in the protocol during the treatment period (V0 to V6). ; Secondary end point(s): The safety and efficacy of BRV will be assessed: - Safety variables include the emergence of a SAEs or TEAEs, withdrawal due to an AE, investigator global evaluation of nonpsychotic behavioural side effects, shift in maximum side effect intensity from baseline to end of treatment, freedom or abatement of nonpsycotice behavioural side effects, laboratory tests (blood chemistry, hematology, urinalysis), vital signs (systolic blood pressure, diastolic blood pressure, heart rate), electrocardiogram (ECG), physical and neurologicals examination. - Efficacy variables include the partial onset seizure (POS) frequency during the treatment period for subjects with focal epilepsy, generalized seizure days during the Treatment Period for subjects with idiopathic generalized epilepsy, investigator and patient global evaluations at the end of the study, and seizure freedom (for all seizure types). | — |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactClin Trial Reg & Results disclosure
UCB BIOSCIENCES GmbH
Outcome results
None listed