E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Medical condition requiring treatment with an AED according to the physician's clinical judgment, and for which the Investigator believes a reasonable benefit from the long-term administration of BRV may be expected. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015037 |
E.1.2 | Term | Epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 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 |
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E.2.2 | Secondary objectives of the trial |
To evaluate the maintenance of efficacy of BRV over time. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 any applicable previous BRV study, 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.
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.
7. Subject must be able to take the oral film-coated tablets of BRV. |
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E.4 | Principal 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, 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. |
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | 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. |
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E.5.2 | 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 partialonset seizure (POS) (Type I) frequency per 28 days during the Evaluation Period. For subjects entering N01372 from a study where Baseline seizure data was collected, secondary efficacy variables for all subjects with epilepsy include 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 all subjects with 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. Other efficacy variables for subjects entering N01372 from a study where Baseline seizure data was collected include the percent reduction in generalized (Type II) seizure days per 28 days from Baseline of the previous study to the Evaluation Period, and the responder rate for generalized (Type II) seizure days over the
Evaluation Period.
Other efficacy variables for subjects entering N01372 from a study where Baseline QOLIE-31-P score was collected, the following will be evaluated separately for subjects with focal-onset epilepsy and subjects with generalized epilepsy: Change in QOLIE-31-P scores from Baseline of the previous study to each assessment for the first 2 years and to the last Evaluation Period assessment during the first 2 years. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | 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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 120 |
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 | No |
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 |
France |
Germany |
Spain |
United States |
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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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Last visit of last subject (LVLS) |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |