E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Electroencephalographic Neonatal Seizures (ENS) |
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E.1.1.1 | Medical condition in easily understood language |
A seizure is a sudden episode of electrical activity in the brain usually for brief period. Seizures in babies can be difficult to recognize. An EEG is needed to confirm a seizure. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 |
Evaluate the efficacy of lacosamide (LCM) versus an Active Comparator chosen based on standard of care (StOC) in severe and nonsevere seizure burden (defined as total minutes of electroencephalographic neonatal seizures (ENS) per hour) in neonates with seizures that are not adequately controlled with previous anti-epileptic drug (AED) treatment |
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E.2.2 | Secondary objectives of the trial |
-Further evaluate the efficacy of lacosamide (LCM) versus an Active Comparator in severe and nonsevere seizure burden (defined as total minutes of electroencephalographic neonatal seizures (ENS) per hour) in neonates with seizures that are not adequately controlled with previous anti-epileptic drug (AED) treatment -Evaluate the short-term safety and tolerability of LCM in neonates -Evaluate the pharmacokinetics (PK) of LCM in neonates who have seizures that are not adequately controlled with previous AED treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Participant must be at least 34 weeks of gestational age (GA) -Participants who have confirmation on video-electroencephalogram (EEG) of ≥2 minutes of cumulative electroencephalographic neonatal seizures (ENS) or ≥3 identifiable ENS prior to entering the Treatment Period -Participants must have received either phenobarbital (PB), levetiracetam (LEV), or midazolam (MDZ) (in any combination) before entering the study -Participant weighs at least 2.3 kg at the time of enrollment Informed consent -An Independent Ethics Committee (IEC)-approved written informed consent form (ICF) is signed and dated by the participant’s parent(s) or legal representative(s) |
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E.4 | Principal exclusion criteria |
-Participant with seizures responding to correction of metabolic disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia) or with seizures for which a targeted, known treatment is available -Participant has seizures related to prenatal maternal drug use or drug withdrawal -Participant has a clinically relevant electrocardiogram (ECG) abnormality, in the opinion of the investigator -Participant receiving treatment with phenytoin (PHT), lidocaine (LDC), or other sodium channel blockers at any time |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in seizure burden measured in the Evaluation video-electroencephalogram (video-EEG) compared with the Baseline video-EEG |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours) |
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E.5.2 | Secondary end point(s) |
1. Percentage of responders in the Evaluation video-EEG compared with the Baseline video-EEG 2. Percentage of participants with at least 80% reduction in seizure burden in the Evaluation a video-EEG compared with the Baseline video-EEG 3. Time to response across the first 48 hours of the Treatment Period compared with the Baseline video-EEG 4. Time to seizure freedom across the first 48 hours of the Treatment Period compared with the Baseline video-EEG 5. Absolute change in seizure burden across the first 48-hours of the Treatment Period measured by continuous video-EEG compared with the Baseline video-EEG 6. Percent change in seizure burden across the first 48-hours of the Treatment Period measured by continuous video-EEG compared with the Baseline video-EEG 7. Percentage of responders at the end of the first 48-hours of the Treatment Period 8. Percentage of study participants who are seizure-free (100% reduction in seizure burden from Baseline) at 24 hours after start of the Treatment Period, categorized by study participants with nonsevere or severe seizure burden at Baseline 9. Categorized percentage change in seizure burden in the Evaluation video-EEG compared with the Baseline video-EEG 10. Percentage of participants with treatment-emergent adverse events (TEAEs) as reported by the investigator 11. Percentage of participants with treatment-emergent marked abnormalities in 12-lead electrocardiogram (ECG) 12. Serum concentration of lacosamide (LCM) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.; 2.; 9. During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours) 3.; 4.; 5.; 6. Across the first 48-hours of the Treatment Period (up to 48 hours) 7. At the end of the first 48-hours of the Treatment Period 8. At 24 hours after start of the Treatment Period, compared with Baseline 10.; 11. From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42) 12. Across the Treatment Period (up to 96 hours) |
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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 | Yes |
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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Active Comparator treatment will be chosen and dosed per local practice and treatment guidelines. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Australia |
Canada |
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.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 21 |