E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 21.0 |
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 objectives of this study are: • To obtain information about the safety, tolerability, and pharmacokinetics (PK) of lacosamide (LCM) during long-term exposure • To obtain preliminary efficacy data on seizure frequency during long term exposure • To allow subjects who have participated in SP847 (or discontinued SP847 due to a dose reduction or status epilepticus) to continue receiving LCM • To allow subjects who have participated in other future LCM pediatric clinical studies in epilepsy to continue receiving LCM • Beginning with Protocol Amendment 4, at selected sites, to allow up to approximately 100 eligible pediatric subjects ≥4 years to ≤17 years of age who have not previously received LCM to begin receiving LCM
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects in SP848 must fulfill the following inclusion criteria: - A signed informed consent form has been obtained from the parent/legal guardian and assent has been obtained from the subject, as required - Subject and caregiver (which may be a parent, legal guardian, or other delegated caregiver) are willing and able to comply with all study requirements, including maintaining a daily seizure diary Subjects who have participated in SP847 or other lacosamide (LCM) pediatric clinical studies in epilepsy must fulfill the following inclusion criteria: - Subject has completed SP847 (or the subject discontinued SP847 due to a dose reduction or status epilepticus) for the treatment of uncontrolled partial-onset seizures, or subject has participated in other LCM pediatric clinical studies in epilepsy - Subject is expected to benefit from participation, in the opinion of the investigator Subjects who enroll directly into SP848 without previous participation in a LCM clinical study must fulfill the following inclusion criteria: - Subject is >=4 years to <=17 years of age - Subject has a diagnosis of epilepsy with partial-onset seizures - Subject has been observed to have uncontrolled partial-onset seizures after an adequate course of treatment (in the opinion of the investigator) with at least 2 Antiepileptic Drugs (AEDs) (concurrently or sequentially) - Subject has been observed to have at least 2 countable seizures in the 4-week period prior to Screening - Subject is on a stable dosage regimen of 1 to 3 AEDs - Subject is an acceptable candidate for venipuncture |
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E.4 | Principal exclusion criteria |
Not permitted to enroll in the study if any of the following criteria are met: - Subject is receiving any investigational drugs or using any experimental devices in addition to lacosamide (LCM) - Subject >= 6 years of age has a lifetime history of suicide attempt, or has suicidal ideation in the past 6 months Subjects who have participated in SP847 or other LCM pediatric clinical studies in epilepsy are not permitted to enroll in the study if any of the following criteria are met: - Subject meets either of the following: a) Withdrawal criteria for the primary study (with the exception of subjects who discontinued due to a dose reduction or status epilepticus). For subjects entering from EP0060, if the subject (or legal guardian) withdraws consent solely due to route of LCM administration (iv) or if the subject requires more than 10 iv LCM infusions, the subject may be allowed to participant in SP848 after discussion with and agreement from the Medical Monitor b) Ongoing serious Adverse Event (SAE) Subjects who enroll directly into SP848 without previous participation in a LCM clinical study are not permitted to enroll in the study if any of the following criteria are met: - Subject has ever received LCM - Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject’s ability to participate in this study. - Subject has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion - Subject has a known hypersensitivity to any component of the investigational medicinal product - Subject is a female of childbearing potential and does not practice an acceptable method of contraception for the duration of the study - Subject has a creatinine clearance less than 30mL/min - Subject has a clinically relevant ECG abnormality, in the opinion of the principal investigator (ie, second or third degree heart block at rest or a QT prolongation greater than 450ms) - Subject has hemodynamically significant heart disease (eg, heart failure) - Subject has an arrhythmic heart condition requiring medical therapy - Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias - Subject has nonepileptic events, including psychogenic seizures, that could be confused with seizures. If both epileptic and nonepileptic events are present, epileptic events must be distinguished from nonepileptic phenomena - Subject has a history of primary generalized epilepsy - Subject is taking monoamine oxidase inhibitors-A (MAOI-A) or narcotic analgesics. - Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease, such as Rasmussen syndrome - Subject has a known sodium channelopathy, such as Brugada syndrome - 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%) Subjects who were directly enrolled in EP0060 for iv LCM replacement therapy or to initiate LCM treatment are not permitted to enroll in the study if any of the following criteria are met: - Subjects have previously participated in a long-term, open-label LCM study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1 - Percentage of participants with treatment-emergent adverse events (TEAEs) 2 - Percentage of participants with serious adverse events (SAEs) 3 - Percentage of participants which withdrew from the study due to TEAEs
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. - 3. Baseline to end of treatment (approximately 2 years)
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E.5.2 | Secondary end point(s) |
1. Percent change from Baseline in 28-day partial-onset seizure frequency 2. Percentage of participants with ≥50% reduction in 28-day partial-onset seizure frequency 3. Percentage of participants with ≥75% reduction in 28-day partial-onset seizure frequency 4. Seizure days per 28 days (subjects with generalized seizures only) 5. Percentage of participants with seizure-free status |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. - 5. Baseline to end of treatment (approximately 2 years) |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
China |
Japan |
Mexico |
Ukraine |
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.8.9.2 | In all countries concerned by the trial years | 11 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 26 |