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 | 20.0 |
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 - Number of subjects who report at least one Treatment-emergent Adverse Event (TEAE)
2 - Number of subjects that withdraw due to a Treatment-emergent AE
3 - For children 18 months to 5 years, the mean change in Achenbach CBCL/11/2 -5 score from Baseline to end of treatment
4 - For children 6 years to 17 years, the mean change in Achenback CBCL/6-18 score from Baseline to end of treatment
5 - For children <18 months, the mean change in Bailey III score from Baseline to end of treatment
6 - For children aged 2 to 4 years, the mean change in BRIEF-P score from Baseline to end of treatment
7 - For children aged 5 to 17 years, the mean change in BRIEF score Baseline to end of treatment
8 - Percentage of subjects with a shift in Tanner Scale score from Baseline to End of Treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-7. Baseline to end of treatment (approximately 2 years)
8. Visit 9; End of treatment (or early discontinuation visit) |
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E.5.2 | Secondary end point(s) |
1. Change from Baseline in seizure frequency
2. Change from Baseline in seizure frequency
3. Mean Clinical Global Impression of Change score
4. Mean Clinical Global Impression of Change score
5. Mean Caregiver Global Impression of Change score
6. Mean Caregiver Global Impression of Change score
7. For children 1 month to 17 years, the mean change in PedsQL health summary score from Baseline to End of treatment
8. LCM Palatability and Ease of Use Questionnaire – Oral Solution
9. LCM Palatability and Ease of Use Questionnaire – Tablets |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline to Visit 9 (approximately 1 year )
2. Baseline to End of treatment (approximately 2 years)
3. Baseline to Visit 9 (approximately 1 year)
4. Baseline to End of treatment (approximately 2 years)
5. Baseline to Visit 9 (approximately 1 year)
6. Baseline to End of treatment (approximately 2 years)
7. Baseline to End of treatment (approximately 2 years)
8. Visit 9; End of treatment (or Early Discontinuation Visit)
9. Visit 9; End of treatment (or Early Discontinuation Visit) |
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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 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
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.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 13 |
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 |