E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Idiopathic generalized epilepsy |
Epilessia idiopatica generalizzata |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071096 |
E.1.2 | Term | Idiopathic generalized epilepsy |
E.1.2 | System Organ Class | 100000004852 |
|
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 demonstrate the efficacy of oral lacosamide (LCM) vs placebo as adjunctive therapy for uncontrolled primary generalized tonic-clonic (PGTC) seizures in subjects with idiopathic generalized epilepsy (IGE) currently taking 1 to 3 concomitant anti-epileptic drugs (AEDs) independent of the number of prior failed AEDs |
Dimostrare l’efficacia di Lacosamide (LCM) somministrato per via orale rispetto al placebo come terapia aggiuntiva per le crisi tonico-cloniche primarie generalizzate (PGTC) incontrollate nei soggetti affetti da epilessia idiopatica generalizzata (IGE) che stanno attualmente assumendo da 1 a 3 farmaci antiepilettici concomitanti (AEDs), indipendentemente dal numero di farmaci antiepilettici assunti in precedenza che non hanno avuto esito positivo nella cura |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of lacosamide (LCM) in subjects with idiopathic generalized epilepsy (IGE) with uncontrolled primary generalized tonic-clonic (PGTC) seizures |
Valutare la sicurezza e la tollerabilità di Lacosamide (LCM) nei soggetti affetti da epilessia idiopatica generalizzata (IGE) con crisi tonico-cloniche primarie generalizzate (PGTC) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject with a confirmed diagnosis at least 24 weeks prior to Visit 1 and a disease onset prior to 30 years of age, consistent with idiopathic generalized epilepsy (IGE) experiencing primary generalized tonic-clonic (PGTC) seizures (Type IIE) that are classifiable according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures (ILAE, 1981).
• Subject has ≥3 PGTC seizures during the 16-week Combined Baseline (12-week Historical Baseline plus 4-week Prospective Baseline)
• If a brain magnetic resonance imaging (MRI)/computed tomography (CT) scan has been performed, there must be no evidence of any progressive abnormality or any lesion likely to be associated with partial-onset seizures.
• Subject has been maintained on a stable dose regimen of 1 to 2 non-benzodiazepine marketed Anti-epileptic drugs (AEDs) OR 1 to 3 AEDs (with at least 1 AED identified as a benzodiazepine) for at least 28 days prior to Visit 1 with or without additional concurrent stable Vagus nerve stimulation (VNS).
• Subjects are required to have had an electroencephalogram (EEG) report consistent with IGE (eg, generalized ≥3Hz epileptiform discharges and a normal EEG background) confirmed by a Central Reviewer. |
• Soggetto con una diagnosi confermata almeno 24 settimane prima della prima visita e con un’insorgenza della malattia prima dei 30 anni, in linea con l’IGE con crisi PGTC (tipo IIE), classificabili secondo la classificazione ILAE relativa alle crisi epilettiche (ILAE, 1981).
• Soggetto con un numero di crisi PGTC ≥3 durante il basale combinato di 16 settimane (basali cronologico di 12 settimane più prospettico di 4)
• Se è stata eseguita una risonanza magnetica (RM) o una tomografia computerizzata (TC) del cervello, non deve essere presente alcuna prova di eventuali anomalie progressive o eventuali lesioni che possono essere associate a crisi parziali.
• Soggetto che abbia mantenuto un regime di dosaggio stabile da 1 a 2 farmaci antiepilettici in commercio senza benzodiazepina O da 1 a 3 farmaci antiepilettici (con almeno 1 farmaco antiepilettico identificato come una benzodiazepina) per almeno 28 giorni prima della prima visita con o senza ulteriore VNS concomitante stabile.
• Referto dell’EEG dei soggetti coerente con l’IGE (ad esempio, scariche epilettiformi generalizzate di ≥3 Hz e un background normale dell’EEG) e confermato da un Revisore centrale. |
|
E.4 | Principal exclusion criteria |
• History of partial onset seizures or EEG findings indicating partial onset seizures
• Symptomatic generalized epilepsy, e.g. Lennox-Gastaut Syndrome
• Lifetime history of suicide attempt, or suicidal ideation in past 6 months
• Women of child bearing potential must practice contraception according to protocol requirements
• Regular use of neuroleptics, narcotics, monoamine oxidase (MOA) inhibitors, barbiturates (for indication other than epilepsy) within 28 days prior to Visit 1
• Use of Felbamate or Vigabatrin within last 6 months
• Subject is on a ketogenic diet |
• Soggetto che abbia una cronologia di crisi parziali o risultati dell’EEG indicativi di crisi parziali.
• Soggetto affetto da epilessia generalizzata sintomatica,ad esempio sindrome di Lennox-Gastaut
• Soggetto che abbia tentato il suicidio o abbia avuto idee suicide nei 6 mesi scorsi
• Le donne in età fertile devono praticare la contraccezione a seconda delle esigenze di protocollo
• Assunzione regolare, entro 28 giorni prima della prima visita di neurolettici, inibitori della monoamino ossidasi (MAO), barbiturici (per indicazioni non relative all’epilessia) o analgesici narcotici.
• Uso di Felbamato o Vigabatrina entro gli ultimi 6 mesi
•Soggetto che stia seguendo una dieta chetogenica. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to the second primary generalized tonic clonic (PGTC) seizure |
Lasso di tempo alla seconda crisi tonico-clonica primaria generalizzata (PGTC) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
24-week Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24) |
Periodo di trattamento di 24 settimane dalla Visita 2 (Settimana 0) alla Visita 10 (Settimana 24) |
|
E.5.2 | Secondary end point(s) |
Seizure freedom for primary generalized tonic clonic (PGTC) seizures
The percent change in primary generalized tonic clonic (PGTC) seizure frequency per 28 days
Time to the first primary generalized tonic clonic (PGTC) seizure
|
Assenza di crisi PGTC
La variazione della percentuale nella frequenza delle crisi PGTC per 28 giorni
Lasso di tempo alla prima crisi tonico-clonica primaria generalizzata (PGTC) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24-week Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
From the Combined Baseline (combined 12-week Historical and 4-week Prospective Baseline) to the first 6 weeks of the Treatment Period
24-week Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24) |
Periodo di trattamento di 24 settimane dalla Visita 2 (Settimana 0) alla Visita 10 (Settimana 24)
Dal basale combinato (basali cronologico di 12 settimane e prospettico di 4) alle prime 6 settimane del periodo di trattamento
Periodo di trattamento di 24 settimane dalla Visita 2 (Settimana 0) alla Visita 10 (Settimana 24) |
|
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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
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 | Information not present in EudraCT |
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 |
Brazil |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Taiwan |
United States |
|
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
|
LVLS |
ultima visita dell'ultimo paziente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 14 |