E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with recently diagnosed partial-onset seizures |
Pacientes adultos con diagnóstico reciente de crisis de comienzo parcial |
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E.1.1.1 | Medical condition in easily understood language |
Adult patients with recently diagnosed partial epilepsy |
Pacientes adultos con diagnóstico reciente de epilepsia parcial |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065336 |
E.1.2 | Term | Partial 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 confirm maintenance of efficacy of eslicarbazepine acetate (ESL, 800 mg to 1600 mg once daily [QD]) monotherapy during long-term treatment in adults (older or equal to 18 years) with recently diagnosed epilepsy experiencing partial-onset seizures. |
Confirmar el mantenimiento de la eficacia del acetato de eslicarbazepina (ESL, 800 mg a 1.600 mg una vez al día [1 v/d]) como monoterapia durante un tratamiento prolongado en adultos (igual o mayor 18 años) con diagnóstico reciente de epilepsia que presentan crisis de comienzo parcial. |
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E.2.2 | Secondary objectives of the trial |
1. To further demonstrate the efficacy of ESL in subjects switching from carbamazepine controlled-release (CBZ-CR) treatment. 2. To demonstrate the safety of ESL in subjects switching from CBZ-CR treatment and in subjects already treated with ESL monotherapy for at least one year (i.e. during long-term treatment). |
1. Demostrar la eficacia de ESL en sujetos que cambian su tratamiento con carbamazepina de liberación controlada (CBZ-LC). 2. Demostrar la seguridad de ESL en sujetos que cambian su tratamiento con CBZ-LC y en sujetos que ya han sido tratados con ESL en monoterapia durante al menos un año (es decir, durante el tratamiento prolongado). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the extension study, subjects must fulfill all of the following at Visit 1 (Day 1, start of the open-label extension study): 1. Participated in the preceding double-blind study and were still ongoing at the time of unblinding. 2. Have signed informed consent before undergoing any activities related to the open-label extension study. 3. Demonstrated cooperation and willingness to complete all aspects of the study. 4. Female subjects without childbearing potential (2 years postmenopausal, bilateral oophorectomy or tubal ligation, or complete hysterectomy) are eligible. Female subjects with childbearing potential must not be pregnant as confirmed by a negative serum ß-human chorionic gonadotropin (hCG) test and sexually active females must be using a medically acceptable effective non-hormonal method of contraception for the duration of the study and until the Post-study Visit (PSV). |
Para la inclusión en el estudio de extensión, los sujetos deben cumplir todos los requisitos siguientes en la visita 1 (día 1, inicio del estudio abierto de extensión): 1.Haber participado en el estudio doble ciego anterior y seguir participando en el momento de la apertura del ciego. 2.Haber firmado un formulario de consentimiento informado antes de la realización de las actividades relacionadas con el estudio abierto de extensión. 3.Haber demostrado disposición y voluntad para completar todos los aspectos del estudio. 4.Las mujeres que no pueden quedarse embarazadas (2 años posmenopáusicas, ooforectomía bilateral o ligadura de trompas, o histerectomía completa) son idóneas. Las mujeres en edad fértil deben obtener un resultado negativo en la prueba de la fracción beta de la gonadotropina coriónica humana (GCH) en sangre para confirmar que no están embarazas, y las mujeres sexualmente activas deben emplear un método anticonceptivo no hormonal eficaz clínicamente aceptable durante el estudio y hasta la visita posterior al estudio (PSV, por sus siglas en inglés). |
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E.4 | Principal exclusion criteria |
Subjects having any of the following at Visit 1 are to be excluded from the study: 1. Excluded from the double-blind study due to seizure in the Maintenance or Extension Phase, or at dose level C (either CBZ-CR or ESL), or discontinued prematurely due to any other reason in the double-blind study. 2. Presence of any major protocol violation during the double-blind study which may have an impact on the compliance during this extension study. 3. Judged clinically to have a suicidal risk in the opinion of the investigator based upon a clinical interview and the Columbia Suicide-Severity Rating Scale (C-SSRS). 4. Occurrence of an adverse event (AE) indicating a suspected presence of atrioventricular block (2nd degree and above) or of any other AEs during the double-blind study which are judged by the investigator as contraindicative to further participation in the open-label extension study. 5. Events of alcohol, drug, or medication abuse during the preceding double-blind study. 6. Relevant clinical laboratory abnormalities (e.g. sodium <125 mmol/L, alanine or aspartate transaminases >2 x the upper limit of normal, white blood cell count <3000 cells/mm3) (as reported at Visit 1). 7. Pregnancy or lactating. 8. Any oth r condition or circumstance that, in the opinion of the investigator, could compromise the subject?s ability to comply with the extension-study protocol. |
Los sujetos serán excluidos del estudio si cumplen cualquiera de los siguientes criterios en la visita 1: 1.Hayan sido excluidos del estudio doble ciego debido a la aparición de crisis en la fase de extensión o mantenimiento, o a un nivel de dosis C (CBZ-LC o ESL), o hayan abandonado el estudio prematuramente por cualquier otro motivo en el estudio doble ciego. 2.La presencia de violaciones importantes del protocolo durante el estudio doble ciego que pueden afectar a su cumplimiento durante el estudio de extensión. 3.Riesgo de suicidio en opinión del investigador en base a una entrevista clínica y al resultado en la escala Columbia para evaluar el riesgo de suicidio (Columbia Suicide-Severity Rating Scale [C-SSRS]). 4.Aparición de un acontecimiento adverso (AA) que indique sospecha de bloqueo auriculoventricular (segundo grado o superior) o cualquier otro AA durante el estudio doble ciego que en opinión del investigador constituya una contraindicación para seguir participando en el estudio abierto de extensión. 5.Episodios de abuso de alcohol, drogas o medicamentos durante el estudio doble ciego anterior. 6.Anomalías en los análisis de laboratorio clínicas relevantes (p. ej., sodio <125 mmol/l, alanina-aminotransferasa o aspartato-aminotransferasa >2 x el límite superior de la normalidad, recuento de leucocitos <3.000 células/mm3) (tal como se informó en la visita 1). 7.Embarazo o lactancia. 8.Cualquier otra enfermedad o circunstancia que, en opinión del investigador, podría comprometer la capacidad del sujeto para completar el protocolo del estudio de extensión. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to treatment failure, defined as time from start of open-label ESL treatment at Visit 1 until withdrawal due to AE or due to lack of efficacy (i.e. inadequate seizure control). |
El tiempo hasta el fracaso terapéutico definido como el tiempo desde el inicio del estudio de extensión hasta la retirada por AA o falta de eficacia (es decir, control inadecuado de las crisis). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at least 1 year |
Al menos un año |
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E.5.2 | Secondary end point(s) |
Treatment retention time (overall, i.e. including previously CBZ-CR treated subjects, and by reason) at the last evaluated dose during open-label treatment, where treatment retention time is defined as the time from start of the extension study until withdrawal of ESL due to AEs or due to lack of efficacy (i.e. inadequate seizure control).
Time to withdrawal for any reason at the last evaluated dose.
Changes in quality of life assessed using the QOLIE-31.
Changes in overall treatment satisfaction as assessed on a 4-point scale. |
Tiempo de retención en el tratamiento (en general, es decir, incluidos los sujetos tratados previamente con CBZ-LC, y por motivo de retirada) en la última dosis evaluada durante el tratamiento sin enmascaramiento, que se define como el tiempo desde el inicio del estudio de extensión hasta la retirada de ESL por AA o falta de eficacia (es decir, control inadecuado de las crisis).
Tiempo hasta la retirada por cualquier motivo en la última dosis evaluada.
Cambios en la calidad de vida según el QOLIE-31.
Cambios en la satisfacción terapéutica global según una escala de 4 puntos. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at least 1 year |
Al menos un año |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Chile |
Croatia |
Czech Republic |
Estonia |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Latvia |
Lithuania |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
Spain |
Sweden |
Ukraine |
United Kingdom |
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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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The complete study duration including treatment with ESL under open-label conditions and follow-up is expected to last approximately 2 years (105 weeks). In case ESL as monotherapy will achieve MA prior to the end of 2017, the study may be discontinued prematurely within 42 days after achievement of MA. |
Se prevé que la duración completa del estudio ? incluido el tratamiento con ESL en abierto y el seguimiento? sea de 2 años aproximadamente (105 semanas).En caso de que la AC de ESL como monoterapia se recibiera antes de finales de 2017, el estudio podría interrumpirse de forma prematura en los 42 días siguientes a la obtención de la AC. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |