E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Focal-Onset Seizures |
Crisis focales |
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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.1.3 | 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 of this study is to evaluate the long-term safety and tolerability of Padsevonil administered at individualized doses as adjunctive treatment for subjects with drug-resistant epilepsy. |
El objetivo principal de este estudio es evaluar la seguridad y tolerabilidad a largo plazo de Padsenovil administrado en dosis personalizadas como tratamiento adyuvante en sujetos con epilepsia fármacorresistente. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the long-term efficacy of Padsevonil as an adjunctive treatment for focal-onset seizures in adults with drug-resistant epilepsy. |
El objetivo secundario es evaluar la eficacia a largo plazo de Pasdenovil como tratamiento adyuvante de crisis focales en adultos con epilepsia fármacorresistente. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject is an adult (18 years of age or more ) - Subject with epilepsy who has completed 1 of the previous Padsevonil (PSL) studies which allow access to the present study - Female subjects of child bearing potential must have a serum negative pregnancy test at the Entry Visit, which is confirmed to be negative by urine testing prior to further dispensing at each study visit thereafter. Subjects will be withdrawn from the study as soon as pregnancy is known. Female subjects will use an efficient form of contraception for the duration of the study and for a period of 3 months after their final dose of PSL. |
- El sujeto es un adulto (tiene ≥18 años de edad) - Sujetos con epilepsia que han completado 1 de los estudios previos sobre el PSL que permiten el acceso al presente estudio. - Las pacientes con capacidad para concebir deben obtener un resultado negativo en la prueba de embarazo en suero en la visita de ingreso al estudio y deberá confirmase este resultado negativo con una prueba de orina antes de continuar con la administración del PSL en cada una de las visitas del estudio posteriores. Se retirará a las pacientes del estudio tan pronto como se conozca el embarazo. Las pacientes utilizarán un método anticonceptivo eficaz durante todo el estudio y durante un periodo de 3 meses tras la última dosis del PSL. |
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E.4 | Principal exclusion criteria |
- Subject has any severe medical, neurological, or psychiatric condition, or laboratory value which may have an impact on the safety of the subject - Subject has active suicidal ideation as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the 'Since Last Visit' version of the Columbia Suicide Severity Rating Scale (C-SSRS) - Subject has >2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (>= l.5x ULN total bilirubin if known Gilbert's syndrome) at the Entry Visit - Subject has a clinically-significant abnormality on electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study - Subject has an abnormality on echocardiogram at last echocardiogram assessment, or foreseen in parent study as assessed by central reader that is accompanied by clinical symptoms or a Grade 2* (or higher)/moderate severity abnormality, or a history of rheumatic heart disease, or other known valvular abnormalities (*according to the ASE Guidelines, 2017; Zoghbi et al 2017) - Female subject who plans to be pregnant or is breastfeeding |
- El sujeto tiene una afección médica, neurológica o psiquiátrica grave o unos valores analíticos que puedan afectar a la seguridad del sujeto. - El sujeto tiene pensamientos suicidas activos, indicados mediante una respuesta afirmativa (“Sí”) a las preguntas 4 o 5 de la versión “desde la última visita” de la escala Columbia para evaluar el riesgo de suicidio (Columbia-Suicide Severity Rating Scale, C-SSRS). - El sujeto tiene más de 2 veces el límite superior de la normalidad (LSN) de cualquiera de los siguientes: alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), fosfatasa alcalina (FA), o >LSN bilirrubina total (≥1,5 veces el LSN de la bilirrubina total si se conoce la presencia del síndrome de Gilbert) en la visita de ingreso en el estudio. - El sujeto tiene cualquier anomalía de importancia clínica presente en el electrocardiograma (ECG) que el investigador considere que puede aumentar los riesgos relacionados con la participación en el estudio. - El sujeto tiene anomalías en el ecocardiograma en la última evaluación por ecocardiograma o previstos en el estudio original según la evaluación del revisor central, acompañados de síntomas clínicos (p. ej.: dificultad para respirar, palpitaciones y soplos) o una anomalía de grado 2 (o superior)/de intensidad moderada, o antecedentes de cardiopatía reumática u otras valvulopatías conocidas. - Pacientes de sexo femenino que planeen quedarse embarazadas o estén en periodo de lactancia. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence of Treatment-Emergent Adverse Events (TEAEs) reported by the subject and/or caregiver or observed by the investigator during the entire study 2. Incidence of Treatment-Emergent Adverse Events (TEAEs) leading to study withdrawal 3. Change in log-transformed observable focal-onset seizure frequency from Baseline over the Evaluation Period |
1. Incidencia de los acontecimientos adversos surgidos durante el tratamiento (AAST) notificados por el sujeto o el cuidador u observados por el investigador. 2. Incidencia de los AAST que provocan la retirada del estudio. 3. Cambio desde el inicio (desde el estudio original respectivo) en la frecuencia de crisis focales observables de acuerdo con la transformación logarítmica a lo largo del periodo de evaluación. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1+2. From Entry Visit (Week 0) until the Safety Follow-up Visit (up to 2 years) 3. From Baseline in respective parent study over the Evaluation Period (minimum of 2 years) |
1+2. Desde la visita de ingreso (semana 0) hasta la visita de seguimiento de la seguridad (hasta 2 años) 3. Desde el inicio (desde el estudio original respectivo) a lo largo del periodo de evaluación (mínimo de 2 años) |
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E.5.2 | Secondary end point(s) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
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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) | Yes |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 96 |
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 |
Belgium |
Bulgaria |
Canada |
Czech Republic |
Germany |
Hungary |
Italy |
Japan |
Mexico |
Poland |
Spain |
Sweden |
United Kingdom |
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 subject last visit (LSLV) |
Última visita último sujeto |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 6 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 6 |