E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065336 |
E.1.2 | Term | Partial epilepsy |
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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 |
to evaluate the efficacy of BRV in the conversion to monotherapy at the doses of 50 and 100 mg/day (administered in two equal doses per day) in subjects with partial onset seizures when compared to a historical pseudo-placebo control group.The primary objective of this study is based on the White Paper on Alternative Monotherapy Design in the Treatment of Epilepsy. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of BRV in subjects undergoing conversion to monotherapy for POS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. An IEC/IRB approved written informed consent signed and dated by the subject or by parent(s) or legal representative. The consent form or a specific assent form, where required, will be signed and dated by minors. 2. Subjects from 16 to 75 years, both inclusive. Subjects under 18 years may only be included where permitted legally and ethically accepted. In Germany, only subjects 18 years and older may be included. 3. Subjects with a body weight ≥ 45 kg. 4. Female subjects without childbearing potential (pre-menarcheal, post-menopausal 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 30 µg [or 50 µg ethinylestradiol per intake if associated with carbamazepine (or other strong enzyme inducers e.g. oxcarbazepine)] must be used in conjunction with a barrier method. 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. Sexual inactivity might be accepted on a case-by-case basis. 5. Subject/legally acceptable representative considered as reliable and capable of adhering to the protocol (e.g. able to understand and complete diaries), Visit schedule or medication intake according to the judgment of the Investigator. 6. Well-characterized partial onset seizures according to the ILAE classification (1981) or focal epilepsy or epileptic syndrome according to the ILAE classification (1989). 7. Presence of an EEG compatible with the clinical diagnosis of focal epilepsy in the last 5 years. If an EEG has not been performed within the last 5 years, a Baseline EEG must be performed before Visit 3. ADDITIONAL INCLUSION CRITERIA ON SYNOPSIS |
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E.4 | Principal exclusion criteria |
1. Seizure type IA simple partial non-motor as only seizure type. 2. History or presence of seizures occurring too frequently or indistinctly separated to be reliably counted, during the 6 months preceding Visit 1 or during Baseline. 3. History or presence of status epilepticus during the 1 year preceding Visit 1 or during Baseline. 4. History or presence of pseudo-seizures. 5. Subjects on felbamate with less than 18 months continuous exposure before Visit 1. Subjects having been on felbamate are eligible if the combined duration of treatment and wash-out is ≥ 18 months. 6. 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. 7. Subjects who have received treatment with phenobarbital or primidone within 3 months prior to Visit 1 and subjects who have received treatment with benzodiazepines within 1 month prior to Visit 1. Subjects with VNS are excluded unless their device has been documented to be inactivated for at least 28 days prior to Visit 1. ADDITIONAL EXCLUSION CRITERIA ON SYNOPSIS |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy end point is the cumulative exit rate at 112 days after the beginning of the tapering phase (at Visit 4) of the Baseline AED(s). |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 32 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |