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 | 13.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10034093 |
E.1.2 | Term | Partial simple seizures NEC |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 long-term safety and tolerability of BRV at individualized doses up to a maximum of 200mg/day
in focal epilepsy subjects. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the maintenance of efficacy of BRV over time. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
An Independent Ethics Committee (IEC)/Institutional Review Board (IRB) approved written informed consent
signed and dated by the subject or by parent(s) or legally acceptable representative. The consent form or a
specific assent form, where required, will be signed and dated by minors.
• Male/female subject from 16 years or older. Subject under 18 years may only be included where legally
permitted and ethically accepted.
• Subject completed the Treatment Period of N01358.
• Subject for whom the Investigator believes a reasonable benefit from the long-term administration of BRV may
be expected.
• Female subject without childbearing potential (premenarcheal, postmenopausal for at least 2 years, bilateral
oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subject 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.
• Subject/legally acceptable representative considered as 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 |
|
E.4 | Principal exclusion criteria |
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 core study
• Severe medical, neurological, or psychiatric disorders, or laboratory values which may have an impact on the
safety of the subject
• Poor compliance with the visit schedule or medication intake in the previous BRV study
• Planned participation in any other clinical study of another investigational drug or device during this study
• Pregnant or lactating woman
• Any medical condition which, in the Investigator’s opinion, warrants exclusion |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• The primary efficacy variable is the POS (type I) seizure frequency standardized to a 28-day duration. This will be summarized by 3-month periods over the Evaluation Period
Secondary efficacy variables
• Seizure frequency per 28 days for all seizure types (I+II+III) by 3-month periods over the Evaluation Period
• Proportion of seizure-free days for all seizure types (I+II+III) by 3-month periods over the Evaluation Period
• Proportion of continuously seizure-free subjects for all seizure types (I+II+III) by 3-month periods over the Evaluation Period
• Responder rate in POS (type I) by 3-month periods over the Evaluation Period. A responder is defined as a subject with a ≥50% reduction in seizure frequency from the Baseline Period for the double-blind study N01358
Other efficacy variables
• Change in QOLIE-31-P scores from the Baseline of N01358 to each assessment for the first 2 years and to the last Evaluation Period assessment during the first 2 years
• Change in HADS scores from the Baseline of N01358 to each assessment for the first 2 years and to the last Evaluation Period assessment during the first 2 years
• Medical resources use during the first 2 years of the Evaluation Period
• Change in socio-professional data from the Baseline of N01358 to each assessment for the first 2 years and to the last Evaluation Period assessment during the first 2 years
II Safety variables
• AEs
• Laboratory tests (including hematology, blood chemistry, urinalysis, and pregnancy test)
• 12-lead ECG
• Physical examination
• Neurological examination
• Vital signs
• Body weight |
|
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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
|
lo studio durera` dall’ingresso nello studio fino a che non sia stata concessa l’approvazione normativa di BRV da un’autorita` sanitaria in un’indicazione ditrattamento aggiuntivo delle POS, finche` lo sponsor non decida di concludere lo studio |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |