E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
highly drug-resistant focal epilepsy |
Epilepsia focal altamente resistente a los medicamentos. |
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E.1.1.1 | Medical condition in easily understood language |
highly drug-resistant focal epilepsy |
Epilepsia focal altamente resistente a los medicamentos. |
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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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065337 |
E.1.2 | Term | Focal epilepsy |
E.1.2 | System Organ Class | 100000004852 |
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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 UCB0942 at individualized doses between 200mg/day to a maximum of 800mg/day in subjects with highly drug-resistant focal epilepsy. |
Evaluar la seguridad y la tolerabilidad a largo plazo de UCB0942 en dosis individualizadas de 200 mg/día hasta un máximo de 800 mg/día en pacientes con epilepsia focal altamente resistente a los medicamentos. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term efficacy of UCB0942 To evaluate the effects of UCB0942 on the subject?s quality of life. |
Evaluar la eficacia a largo plazo de UCB0942. Evaluar los efectos de UCB0942 en la calidad de vida de los pacientes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A written Informed Consent form approved by the Independent Ethics Committee is signed and dated by the subject, after the Investigator assesses whether the subject is able to understand the potential risks and benefits of participating in the study Subject must have completed V13 of the Outpatient Maintenance Period of EP0069 to be eligible for enrollment into EP0073 In EP0069, the subject demonstrated a reduction in frequency and/or severity of seizures as compared to baseline that is considered clinically significant by the Investigator and significant by the subject In EP0069, the subject experiences substantial benefit from UCB0942 with acceptable tolerability according to the subject and Investigator No tolerability issues that can outweigh attained benefits, in the opinion of the Investigator ? Female subjects of nonchildbearing potential (premenarcheal, postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, and complete hysterectomy) are eligible. Female subjects of childbearing potential are eligible if they use medically accepted contraceptive methods. Male subject confirms that, during the study period and for a period of 3 months after the final dose, when having sexual intercourse with a woman of childbearing potential, he will use a barrier contraceptive (eg, condom) AND that the respective partner will use an additional contraceptive method |
El participante firma y fecha un consentimiento informado por escrito aprobado por el CEI una vez que el investigador determina si el participante puede comprender los riesgos y beneficios de la participación en el estudio. El paciente debe haber completado la V13 del período de mantenimiento ambulatorio de EP0069 para ser apto para la inscripción en EP0073. En EP0069, el paciente presenta una reducción de la frecuencia o la gravedad de las crisis en comparación con la situación inicial clínicamente significativa según el investigador y el paciente. En EP0069, el paciente se beneficia considerablemente de UCB0942 con una tolerabilidad aceptable según el paciente y el investigador. No se producen problemas de tolerabilidad de mayor importancia que los beneficios obtenidos en opinión del investigador. Las mujeres sin posibilidad de quedarse embarazadas (premenárquicas, posmenopáusicas durante 2 años como mínimo o sometidas a una ooforectomía bilateral, una ligadura de trompas o una histerectomía total) son aptas. Las mujeres con posibilidad de quedarse embarazadas son aptas si usan métodos anticonceptivos aceptados desde el punto de vista médico. Los hombres deben confirmar que, durante el período del estudio y durante un período de 3 meses después de la dosis final, en caso de tener relaciones sexuales con una mujer con posibilidad de quedarse embarazada, usarán un anticonceptivo de barrera (por ejemplo, preservativos) Y que su pareja usará un método anticonceptivo adicional. |
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E.4 | Principal exclusion criteria |
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. The subject should be referred immediately to a Mental Healthcare Professional and must be withdrawn from the study Subject has taken other (non-Anti-Epileptic Drug) prescription, non-prescription, dietary (eg, grapefruit or passion fruit), or herbal products that are potent inducers or inhibitors of the CYP3A4 pathway for 2 weeks (or 5 half lives whichever is longer) prior to study entry ? Subject has an abnormality in the 12-lead electrocardiography that, in the opinion of the Investigator, increases the risks associated with participating in the study. In addition, any subject with any of the following findings will be excluded: - Prolonged QTc (Bazett?s, machine-read) interval defined as > 450 ms for males and > 470 ms for females - Bundle branch blocks and other conduction abnormalities other than mild first degree atrioventricular block (defined as PR interval >= 220 ms) - Irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular or rare ventricular ectopic beats - In the judgment of the Investigator, T-wave configurations are not of sufficient quality for assessing QT interval duration. Subject has a clinically significant abnormality on echocardiography at the Entry Visit (V2) of EP0073 |
El paciente tiene ideas de suicidio actualmente de acuerdo con una respuesta positiva («sí») a la pregunta 4 o la pregunta 5 de la versión «desde la última visita» de C-SSRS. El paciente debe ser derivado de inmediato a un profesional de salud mental y retirado del estudio. El paciente ha tomado otros productos (distintos de los FAE) con receta o sin receta, alimenticios (por ejemplo, pomelo o fruta de la pasión) o de fitoterapia que son potentes inductores o inhibidores de la vía CYP3A4 durante 2 semanas (o 5 semividas [el valor superior]) antes de la inclusión en el estudio. El paciente presenta una anomalía en el ECG de 12 derivaciones que, en opinión del investigador, aumenta los riesgos asociados a la participación en el estudio. Además, se excluirá a los pacientes con cualquiera de los siguientes hallazgos: Intervalo QTc prolongado (fórmula de Bazett, detección con aparato) definido como >450 ms en hombres y >470 ms en mujeres. Bloqueos de rama y otras anomalías de la conducción distintas del bloqueo auriculoventricular de primer grado leve (definidos como un intervalo PR >=220ms) Ritmos irregulares distintos de la arritmia sinusal o supraventricular ocasional o infrecuente, o la extrasístole ventricular infrecuente. Según el criterio del investigador, las ondas T no tienen la calidad suficiente para evaluar la duración del intervalo QT. El paciente presenta una anomalía clínicamente significativa en la ecocardiografía en la VI (V2) de EP0073. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The 75% Responder Rate at the end of the Evaluation Period Number of subjects with at least one treatment-emergent Adverse Events during the EP0073 study Number of subjects with at least one Serious Adverse Event during the EP0073 study Number of subjects discontinued due to treatment-emergent Adverse Events during the EP0073 study |
Índice de mejora del 75 % al final del Período de Evaluación Número de pacientes con por lo menos un acontecimiento adverso emergente durante el tratamiento, durante el estudio EP0073. Número de pacientes con al menos un Acontecimiento Adverso Grave durante el estudio EP0073. Número de pacientes que han discontinuado durante el estudio EP0073 debido a Acontecimientos Adversos Graves debidos al tratamiento. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Median partial-onset seizure frequency per 28 days over the Evaluation Period of the EP0073 study Median partial-onset seizure frequency per 28 days by seizure type over the Evaluation Period of the EP0073 study Percent reduction in partial-onset seizure frequency relative to the 2-week Prospective Outpatient Baseline Period defined in EP0069 over the Evaluation Period of the EP0073 study The 50 % responder rate over the Evaluation Period of the EP0073 study Percentage of seizure-free days over the Evaluation Period Seizure-free rate over the Evaluation Period Changes in Quality of Life in Epilepsy 31-P (QOLIE-31-P) total scores from Visit 3 (Week 2) of EP0069 through the assessment of the Evaluation Period |
Frecuencia media de CPI por 28 días en intervalos de tres meses durante el período de evaluación del estudio EP0073. Frecuencia media de CPI por 28 días por tipo de crisis durante el período de evaluación del estudio EP0073. Porcentaje de reducción de la frecuencia de CIP en relación con el período inicial ambulatorio prospectivo de 2 semanas establecido en EP0069 durante el período de evaluación del estudio EP0073. Tasa de respuesta del 50% durante el Período de Evaluación del estudio EP0073 Porcentaje de días sin crisis durante el Período de Evaluación. ïndice de ausencia de crisis durante el Período de Evaluación. Cambios en las puntuaciones de QOLIE-31-P desde la V3 de EP0069 durante el período de evaluación. |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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) | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |