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 |
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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 | 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 |
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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 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 |
|
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 |
|
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) with no benzodiazepine AEDs OR 1 benzodiazepine marketed AED with 1 to 2 non-benzodiazepine marketed AEDs 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. |
|
E.4 | Principal exclusion criteria |
• Subject is receiving any investigational drugs or using any experimental devices in addition to Lacosamide (LCM)
• Subject meets the withdrawal criteria for SP0982 or is experiencing an ongoing serious adverse event (SAE)
• 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 (>=1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie. direct bilirubin <35%)
• History of partial onset seizures or EEG findings indicating partial onset seizures
• Symptomatic generalized epilepsy, e.g. Lennox-Gastaut Syndrome typically presenting with seizures including tonic seizures), some other related syndrome like Doose's syndrome (typically presenting with myoclonic-atonic seizures) or evidence of both focal and generalized epilepsy.
• 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 clozapine, 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 that has either changed within the 4 weeks prior to Visit 1 or is expected to change during the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to the second primary generalized tonic clonic (PGTC) seizure |
|
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) |
|
E.5.2 | Secondary end point(s) |
Seizure freedom for primary generalized tonic clonic (PGTC) seizures
Time to the first primary generalized tonic clonic (PGTC) seizure
Incidence of Treatment Emergent Adverse Events (TEAEs) as reported spontaneously by the subject and/or caregiver or observed by the investigator
Incidence of Serious Adverse Events (SAEs) as reported spontaneously by the subject and/or caregiver
or observed by the investigator |
|
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)
During Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
From Visit 1 (Week 4) to End of Study Period (up to Week 36)
From Visit 1 (Week 4) to End of Study Period (up to Week 36) |
|
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Belgium |
Brazil |
Bulgaria |
China |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Poland |
Portugal |
Romania |
Russian Federation |
Slovakia |
Spain |
Taiwan |
Turkey |
United States |
|
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
|
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |