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 | 18.1 |
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 |
To evaluate the safety and tolerability of intravenous (iv) lacosamide (LCM) infusion(s) in subjects ≥4 to <17 years of age with epilepsy, after temporarily switching from the equivalent stable oral LCM dose. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetics (PK) of intravenous (iv) lacosamide (LCM) replacement in pediatric subjects with epilepsy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is male or female from ≥4 to <17 years of age. 2. Subject is participating in a long-term, open-label study with lacosamide (LCM) or is currently prescribed oral VIMPAT and needs to undergo a procedure, is admitted to an epilepsy monitoring unit (EMU) or health care facility, or other situations where intravenous (iv) administration of LCM is clinically appropriate. 3. Subject is an acceptable candidate for venipuncture and iv infusion. Subjects who are participating in a long-term, open-label study with LCM must fulfill the following additional inclusion criteria: 4. Subject is currently enrolled in a long-term, open-label study, receiving oral LCM for the treatment of epilepsy. 5. Subject has been on a stable bid dosage regimen of oral LCM for the last 3 days in their long-term, open-label study. Subjects who are currently prescribed oral VIMPAT and enroll directly into EP0060 must fulfill the following additional inclusion criteria: 6. Subject has been prescribed oral VIMPAT at a dose of 2mg/kg/day to 12mg/kg/day (for subjects <50kg) or 100mg/day to 600mg/day (for subjects ≥50kg). 7. Subject has been prescribed oral VIMPAT for the treatment of epilepsy for at least 1 month prior to Screening and has not been prescribed or maintained on VIMPAT for the purposes of participating in EP0060. Prescribed oral VIMPAT dose must be stable for at least 7 days, and intake of the prescribed total daily dose confirmed for at least 3 days prior to first infusion.
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E.4 | Principal exclusion criteria |
1. Subject has previously received intravenous (iv) lacosamide (LCM) in this study. 2. Subject has any medical, neurological, or psychiatric condition that, in the opinion of the investigator, could jeopardize the subject’s health or compromise the subject’s ability to participate in EP0060. 3. Subject has clinically significant hypotension or bradycardia. 4. Subject ≥6 years of age has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by positive responses (“Yes”) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening. 5. Subject does not have a diagnosis of epilepsy. 6. Subject is taking monoamine oxidase inhibitors (MAOIs). Subjects who are participating in a long-term, open-label study with LCM are not permitted to enroll in EP0060 if any of the following additional criteria are met: 7. Subject has any ongoing Adverse Event (AE) in their long-term, open-label study that, in the opinion of the investigator, could jeopardize or would compromise the subject’s ability to participate EP0060. Subjects who are currently prescribed oral VIMPAT are not permitted to directly enroll in EP0060 if any of the following additional criteria are met: 8. Subject has a medical condition that could reasonably be expected to interfere with drug distribution, metabolism, or excretion. 9. Subject has a known hypersensitivity to any component of the investigational medicinal product (IMP). 10. Subject is a female of childbearing potential and does not practice an acceptable method of contraception for the duration of participation in EP0060. 11. Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin level greater than or equal to 2 times the upper limit of normal (ULN), or creatinine clearance less than 30mL/min. 12. Subject has a clinically relevant electrocardiogram (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). 13. Subject has hemodynamically significant heart disease (eg, heart failure). 14. Subject has an arrhythmic heart condition requiring medical therapy. 15. Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias. 16. Subject has only nonepileptic events, including psychogenic seizures, which could be confused with seizures. If both epileptic and nonepileptic events are present, epileptic events must be distinguished from nonepileptic phenomena. 17. Subject has been treated with felbamate for at least 12 months prior to entering EP0060 and has experienced any toxicity issues with this treatment. Note: Any subject who is currently treated with felbamate, and has received felbamate for a period of less than 12 months, is excluded from EP0060. 18. Subject has an acute or subacutely progressive central nervous system disease. Subject has epilepsy secondary to a progressing cerebral disease or any other progressive or neurodegenerative disease (malignant brain tumor or Rasmussen syndrome). 19. Subject has a known cardiac sodium channelopathy, such as Brugada syndrome. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Number of subjects that withdraw due to treatment emergent adverse events during the study 2)Number of subjects experiencing at least one treatment emergent adverse event during the study 3) Number of subjects experiencing at least 1 injection-related treatment emergent adverse event during the study
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) During the treatment period (up to 5 days) 2) During the treatment period (up to 9 days) 3) During the treatment period (up to 5 days)
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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 | No |
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 | 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) | 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 | 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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Croatia |
France |
Georgia |
Hungary |
Italy |
Mexico |
Poland |
Spain |
Thailand |
United States |
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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
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 9 |
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 | 15 |