| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10034093 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to evaluate the efficacy of BRV at doses of 100 and 200mg/day compared to placebo (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. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective is to assess the safety and tolerability of BRV. Exploratory objectives are to assess the effects of BRV on subjects’ Health-related Quality of Life (HRQoL), to obtain a description of the patients’ self-reported health status, and explore direct medical resources use. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 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. 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. 4. Subjects with a body weight ≥40kg. 5. 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. 6. Well-characterized focal epilepsy/epileptic syndrome according to the 1989 International League Against Epilepsy (ILAE) classification. 7. Presence of an EEG reading compatible with the clinical diagnosis of focal epilepsy within the last 5 years. 8. Presence of a brain MRI/computed tomography (CT) scan performed within the last 2 years. 9. 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. UCB 27-September-2010 Protocol Summary Brivaracetam N01358 Confidential Page 9 of 19 10. Subjects having at least 2 partial onset seizures whether or not secondarily generalized per month during the 3 months preceding V1. 11. 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. 12. 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. |
|
| E.4 | Principal exclusion criteria |
Subject previously randomized within this study or any other prior study with BRV.• Seizure type IA non motor as only seizure type. • Subject has participated in another study of an investigational medication.• Subject is currently treated with LEV.• Subject has taken LEV within 90 days prior to V1.• Subject has any medical or psychiatric condition that.• Subject has a known hypersensitivity to any components of the investigational medicinal product orcomparative drugs as stated in this protocol.• Subject not able to read and understand the informed consent form, assent form, or seizure diary cardinstructions.• Subject has obvious cognitive impairment or mental retardation • Subjects whose seizures could not be reliably.• 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) • Subject taking any drug that may significantly influence the metabolism of BRV cytochrome P450. • Subject has history of cerebrovascular accident, • Subject is suffering from severe cardiovascular disease or peripheral vascular disease • Subject has presence of any sign (clinical or imaging techniques) suggesting rapidly progressing brain disorder or brain tumor.. • Subject has any clinical conditions (eg, bone marrow depression, chronic hepatic disease, and/or severe renal impairment). • 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, AST/SGOT, 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. parameters: creatinine clearance calculated <30mL/min, platelets <100,000/μL, or neutrophil cells <1,800/μL.
• Subject has clinically significant ECG abnormalities according to the Investigator. • Subject has history of suicide attempt prior to randomization. • Subject has ongoing psychiatric disease other than mild controlled disorder. • Subject has known allergic reaction or intolerance to pyrrolidine derivatives and/or investigational product excipients. • Subject has known multiple drug allergies or severe drug allergy. • Subject is pregnant or lactating woman. • Subject has known alcohol or drug addiction or abuse within the last 2 years. • Investigators, co-Investigators, their spouses or children, or any study collaborators. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable is the POS (Type I) frequency per 28 days during the 12-week Treatment Period. The primary efficacy outcome for the USA will be the percent reduction in POS (Type I) frequency over PBO based on ANCOVA. The primary efficacy outcome for European authorities will be the 50% responder rate based on percent reduction in POS (Type 1) frequency from Baseline to the 12-week Treatment Period. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 80 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| la fine dello studio e` definita come data dell`ulima visita dell`ulimo paziente |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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