E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epilepsy with partial onset seizures |
Epilepsia con crisis de inicio parcial |
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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 | 14.1 |
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 |
The primary objective of this study is to assess the overall effectiveness of LCM (optimized within the range of 200mg/day to 600mg/day) when added to a stable dose of LEV (in the label range of 1000mg/day to 3000mg/day) with withdrawal of the concomitant SCB-AED in subjects with partial-onset seizures not adequately controlled on their dual LEV and SCB-AED regimen. |
El objetivo principal del estudio es evaluar la efectividad global de la LCM (con una dosis optimizada entre los 200 mg y los 600 mg al día) cuando se añade a una pauta estable de LEV (dosis según ficha técnica, de entre 1000 mg y 3000 mg al día) y se retira el antiepiléptico BCS concomitante, en sujetos con crisis convulsivas de inicio parcial que no están bien controladas con la biterapia de LEV y el BCS. |
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E.2.2 | Secondary objectives of the trial |
Other objectives of this study are to evaluate seizure reduction during the study versus Baseline and to evaluate the safety of LCM when LCM (optimized within the range of 200mg/day to 600mg/day) is added to LEV (in the label range of 1000mg/day to 3000mg/day) with withdrawal of the concomitant SCB-AED in subjects with partial-onset seizures not adequately controlled on their dual SCB-AED and LEV regimen. |
Otros objetivos del estudio son determinar la reducción de las crisis respecto a la frecuencia basal y la seguridad de la LCM (con una dosis optimizada entre los 200 mg y los 600 mg al día) cuando se añade a una pauta estable de LEV (dosis de entre 1000 mg y 3000 mg al día) y se retira el antiepiléptico BCS concomitante, en sujetos con crisis convulsivas de inicio parcial que no están bien controladas con la biterapia de LEV y el BCS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is male or female, at least 18 years of age. 2. Subject has a diagnosis of epilepsy with partial-onset seizures according to the International Classification of Epileptic Seizures (1981). 3. Subject is taking LEV in combination with 1 sodium channel blocking antiepileptic drug (defined as carbamazepine, lamotrigine, oxcarbazepine, phenytoin, or eslicarbazepine) as adjunctive treatment for epilepsy. 4. The minimum required seizure frequency during the 8-week Retrospective Seizure Baseline is on average at least2 partial-onset seizures per 28 days with at least 1 seizure per 4 week period within the 8-week Retrospective Seizure Baseline. Additionally, subjects must experience at least 1 seizure during the 4-week Prospective Seizure Baseline. 5. Subject has been maintained on a stable dose of LEV and a sodium channel blocking antiepileptic drug for at least 4 weeks prior to the Screening Visit (Visit 1) and during the 4-week Prospective Seizure Baseline. 6. The minimum required seizure frequency during the 8-week Retrospective Seizure Baseline is on average at least 2 partial-onset seizures (IA, IB, or IC) per 28 days (based on investigator assessment of subject report) with at least 1 seizure per 4 week period within the 8-week Retrospective Seizure Baseline. 7. Subject has been maintained on a stable dose of LEV and a SCB-AED for at least 4 weeks prior to the Screening Visit (Visit 1) and during the 4-week Prospective Seizure Baseline, with or without additional concurrent stable vagal nerve stimulation (VNS). The VNS must have been in place for at least 6 months prior to the Screening Visit (Visit 1) with constant settings for at least 4-weeks prior to the Screening Visit (Visit 1) and throughout the duration of the study. |
1. Sexo masculino o femenino y al menos de 18 años de edad. 2. Diagnóstico de epilepsia con crisis de inicio parcial según la clasificación internacional de las crisis epilépticas (1981). 3. Tratamiento actual contra la epilepsia con LEV en combinación con un antiepiléptico BCS (carbamazepina, lamotrigina, oxcarbazepina, fenitoína o eslicarbazepina) como adyuvante. 4. Frecuencia mínima de crisis convulsivas, durante el período basal retrospectivo de 8 semanas, de promedio de al menos 2 crisis parciales (IA, IB ó IC) por 28 días (según determine el investigador a partir de lo referido por el sujeto) y al menos 1 crisis por período de 4 semanas; además, al menos 1 crisis durante el período basal prospectivo de 4 semanas. 5. Mantenimiento de la dosis inalterada de LEV y del BCS durante las 4 semanas anteriores a la visita de selección (visita 1) y durante las 4 semanas del período basal prospectivo. 6. La frecuencia mínima requerida durante el ataque inicial de convulsiones de 8 semanas retrospectiva es, en promedio al menos 2 crisis de inicio parcial (IA, IB o IC) en 28 días (basado en la evaluación del investigador del informe de sujetos) con al menos un ataque por 4 semanas período de referencia dentro de la retrospectiva de 8 semanas de convulsiones. 7. Una vez se ha mantenido en una dosis estable de LEV y un AED SCB-por lo menos 4 semanas antes de la visita de selección (Visita 1) y en la inicial de convulsiones de 4 semanas prospectivo, con o sin estimulación adicional concurrentes estable del nervio vago (VNS). La estimulación del nervio vago que han estado en vigor durante al menos 6 meses antes de la visita de selección (Visita 1) con la configuración de constante durante al menos 4 semanas antes de la visita de selección (Visita 1) y durante toda la duración del estudio. |
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E.4 | Principal exclusion criteria |
1. Previous use of lacosamide. 2. History of alcohol or drug abuse. 3. History of seizure disorder characterized primarily by isolated auras. 4. History of primary generalized seizures. 5. History of status epilepticus within the 12-months. 6. History of clustering seizures. 7. Nonepileptic events, including pseudoseizures that could be confused with seizures 8. History of any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize the subject's health or would compromise the subject's ability to participate in this study. 9. Lifetime history of suicide attempt,or suicidal ideation in the past 6 months. 10. Hypersensitivity to any component of LCM. 11. History of acute or sub-acute progressive central nervous system disease. 12. History of severe anaphylactic reaction or serious blood dyscrasias. 13. Impaired renal function (ie, creatinine clearance [CLcr] is lower than 30mL/min) at Visit 1. 14. History of sick sinus syndrome without a pacemaker, or atrioventricular (AV) block, or subject has any other clinically significant ECG abnormalities. 15. History sodium channelopathy, such as Brugada syndrome. 16. History of myocardial infarction in the last 3 months. |
1.Exposición anterior a la LCM. 2.Antecedentes de toxicomanía o alcoholismo 3.Trastorno convulsivo caracterizado principalmente por auras aisladas 4.Antecedentes de crisis primarias generalizadas. 5.Antecedentes de estado epiléptico en los 12 meses anteriores 6.Número incontable de crisis debido a su cercanía en el tiempo 7.Antecedentes o diagnóstico actual de crisis pseudoepilépticas, trastornos de conversión u otras crisis de carácter no epiléptico que puedan confundirse con convulsiones 8. Enfermedad física o psiquiátrica que, a juicio del investigador, ponga en entredicho la salud del sujeto o su capacidad de participar en el estudio 9.Antecedentes de intento de suicidio o ideas suicidas en los últimos 6 meses. 10.Hipersensibilidad a cualquiera de los ingredientes de los comprimidos de LCM. 11.Enfermedad progresiva del sistema nervioso central, de carácter agudo o subagudo. 12.Antecedentes de reacción anafiláctica grave o discrasias sanguíneas graves. 13.Disfunción renal (aclaramiento de creatinina [AclCr] por debajo de 30 ml/min) en la visita 1. 14.Disfunción sinusal sin marcapasos, bloqueo auriculoventricular u otras alteraciones electrocardiográficas de relevancia clínica. 15.Canalopatía del sodio, p. ej. síndrome de Brugada. 16.Infarto de miocardio en los últimos 3 meses. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the retention at the end of the 21-week treatment period. |
La variable principal es determinar la efectividad global, es la tasa de retención del período de tratamiento de 21 semanas. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The timepoint of evaluation is at end of the treatment period (21 weeks). |
El momento de evaluación es el final del periodo de tratamiento (21 semanas) |
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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 | 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 | 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 |
Australia |
Austria |
Bulgaria |
Canada |
Denmark |
France |
Germany |
Netherlands |
Romania |
Spain |
Sweden |
Switzerland |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |