Trial Outcomes & Findings for A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures (NCT NCT04519645)

NCT ID: NCT04519645

Last Updated: 2025-10-03

Results Overview

Baseline seizure burden was defined as seizure burden measured on the continuous video-EEG (total electroencephalographic neonatal seizures (ENS) in minutes per hour) during a period of up to 2 hours immediately prior to the first administration of study drug. An ENS was defined as an EEG seizure lasting for at least 10 seconds on video-EEG. The seizure burden in the Evaluation Period was calculated as the total duration of seizures between 1 and 3 hours after the first dose of study medication divided by the duration of interpretable video-EEG available in the same period. Change in seizure burden measured in the Evaluation video-EEG compared with the Baseline video-EEG was analyzed such that a positive value indicates a reduction in seizure burden from baseline.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline

Results posted on

2025-10-03

Participant Flow

The study started to enrol participants in March 2021 and concluded in October 2024.

The Participant Flow refers to the Safety set. This study was ended after agreed Pediatric investigation plan (PIP) modification, not linked to safety reasons.

Participant milestones

Participant milestones
Measure	No Treatment Participant signed the informed consent form, successfully screened and randomized but never received any study medication during the study.	Active Comparator Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Enrollment Period (Up to 36 Hours) STARTED	3	11	15
Enrollment Period (Up to 36 Hours) COMPLETED	0	11	15
Enrollment Period (Up to 36 Hours) NOT COMPLETED	3	0	0
Treatment Period (Up to 96 Hours) STARTED	0	11	15
Treatment Period (Up to 96 Hours) Safety Set (Actual Treated)	0	12	14
Treatment Period (Up to 96 Hours) Full Analysis Set (Treated as Randomized)	0	9	15
Treatment Period (Up to 96 Hours) COMPLETED	0	10	15
Treatment Period (Up to 96 Hours) NOT COMPLETED	0	1	0
Extension Period: up to 28 Days of PNA STARTED	0	0	12
Extension Period: up to 28 Days of PNA COMPLETED	0	0	12
Extension Period: up to 28 Days of PNA NOT COMPLETED	0	0	0
Safety Follow Up Period: 14 Days STARTED	0	10	15
Safety Follow Up Period: 14 Days COMPLETED	0	10	15
Safety Follow Up Period: 14 Days NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	No Treatment Participant signed the informed consent form, successfully screened and randomized but never received any study medication during the study.	Active Comparator Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.
Enrollment Period (Up to 36 Hours) Adverse Event	1	0
Enrollment Period (Up to 36 Hours) Withdrawal by Parent/Guardian	1	0
Enrollment Period (Up to 36 Hours) Protocol Violation	1	0
Treatment Period (Up to 96 Hours) Consent withdrawn by parent/guardian,not due to AE	0	1

Baseline Characteristics

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Comparator n=12 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=14 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.	Total n=26 Participants Total of all reporting groups
Age, Continuous	3.1 days STANDARD_DEVIATION 2.8 • n=5 Participants	4.1 days STANDARD_DEVIATION 5.0 • n=7 Participants	3.7 days STANDARD_DEVIATION 4.1 • n=5 Participants
Age, Customized 0-<=27 days	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other or Mixed	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline

Population: The Full Analysis Set (FAS) consisted of all study participants in the SS who had a minimum of 30 minutes of interpretable video-EEG data from both Baseline and the period between 1 and 3 hours (Evaluation Period) after randomization to the initial study medication treatment. The FAS population was based on randomized treatment. Here, overall number of participants analyzed included all participants who were evaluable for this assessment.

Outcome measures

Outcome measures
Measure	Active Comparator n=9 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=11 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Change in Seizure Burden Measured in the Evaluation Video-electroencephalogram (Video-EEG) Compared With the Baseline Video-EEG	2.45 minute per hour (min/hour) Standard Deviation 14.83	6.64 minute per hour (min/hour) Standard Deviation 6.55

SECONDARY outcome

Timeframe: During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline

Population: The FAS consisted of all study participants in the SS who had a minimum of 30 minutes of interpretable video-EEG data from both Baseline and the period between 1 and 3 hours (Evaluation Period) after randomization to the initial study medication treatment. The FAS population was based on randomized treatment.

A responder is defined as a study participant who achieved the following reduction in seizure burden without need for rescue medication, compared with the seizure burden measured during the Baseline Period immediately prior to the study medication administration, evaluated for a 2-hour period starting 1 hour after the start of initial treatment: - At least 80% reduction of seizure burden in participants who were categorized by the Investigator as having non-severe seizure burden during Baseline OR - At least 50% reduction of seizure burden in participants who were categorized by the Investigator as having severe seizure burden during Baseline.

Outcome measures

Outcome measures
Measure	Active Comparator n=9 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=15 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Percentage of Responders in the Evaluation Video-EEG Compared With the Baseline Video-EEG	66.7 percentage of participants	60.0 percentage of participants

SECONDARY outcome

Timeframe: During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline

A responder is defined as a study participant who achieved the following reduction in seizure burden without need for rescue medication, compared with the seizure burden measured during the Baseline Period immediately prior to investigational medicinal product (IMP) administration, evaluated for a 2-hour period starting 1 hour after the start of initial treatment: A reduction in seizure burden from Baseline of \>=80% regardless of baseline seizure severity. Percentage of Participants With at least 80% Reduction in Seizure Burden in the Evaluation (starting 1 hour after treatment) of a Video-EEG Compared with the Baseline Video-EEG were reported.

Outcome measures

Outcome measures
Measure	Active Comparator n=9 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=15 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Percentage of Participants With at Least 80% Reduction in Seizure Burden in the Evaluation a Video-EEG Compared With the Baseline Video-EEG	44.4 percentage of participants	60.0 percentage of participants

SECONDARY outcome

Timeframe: Across the first 48 hours of Treatment Period, compared to Baseline

Time to response where response was defined as a reduction in seizure burden from Baseline of at least 80% in participants with non-severe seizure burden, and of at least 50% for participants with severe seizure burden. Time to response was censored at the date/time the participant received rescue medication or stopped video-EEG monitoring, or otherwise at the end of the 48-hour period.

Outcome measures

Outcome measures
Measure	Active Comparator n=9 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=15 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Time to Response Across the 48-hour Treatment Period Compared With the Baseline Video-EEG	3.0 hours Interval 3.0 to 8.0	3.0 hours Upper and lower limits of 95% confidence interval could not be calculated by the Kaplan-Meier model due to heavy censoring occurring before the median survival time was observed and a lack of variability in the response times (9/10 patients reported the same time to response).

SECONDARY outcome

Timeframe: Across the first 48 hours of Treatment Period, compared to Baseline

Seizure freedom was defined as 0 minutes of seizures in a 1-hour period (or 2-hour period for the 3-hour time point) and was analyzed across the 48 hours. The time to seizure freedom was measured in hours, defined as the first time point when the response criterion was met minus the date and time of the first dose of randomized study medication administration. Time to seizure freedom was censored at the time of receiving rescue medication, stopping video-EEG monitoring or otherwise at 48 hours after first dose.

Outcome measures

Outcome measures
Measure	Active Comparator n=9 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=15 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Time to Seizure Freedom Across the First 48-hour Treatment Period Compared With the Baseline Video-EEG	8.0 hours Interval 3.0 to Upper limit of 95% confidence interval could not be calculated by the Kaplan-Meier model due to heavy censoring occurring before the median survival time was observed and a lack of variability in the response times (4/6 patients reported the same time to seizure freedom).	3.0 hours Upper and lower limits of 95% confidence interval could not be calculated by the Kaplan-Meier model due to heavy censoring occurring before the median survival time was observed and a lack of variability in the response times (9/10 patients reported the same time to seizure freedom).

SECONDARY outcome

Timeframe: Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline

Population: FAS consisted of all study participants in the SS who had a minimum of 30 minutes of interpretable video-EEG data from both Baseline and the period between 1 and 3 hours (Evaluation Period) after randomization to the initial study medication treatment. FAS population was based on randomized treatment. Here, overall number of participants analyzed included all participants who were evaluable for this assessment and number analyzed signifies participants who were evaluable at specified timepoints.

Baseline seizure burden was calculated as total duration of seizures (in minutes) between -2 hour and 0 hours before first dose of study medication divided by total duration of interpretable video-EEG (in hours) in the same period. Seizure burden for 8, 16, 24, 32, 40 and 48 hour time points was calculated as total duration of seizures in the hour prior to time point divided by duration of interpretable video-EEG available in same period. If \<30 minutes of interpretable video-EEG were available in the 1 hour prior to the time point, response was calculated based on seizure burden for most recent 30 minutes of interpretable video-EEG in the 2 hours (for 8 and 16 hour points) or 4 hours (for 24, 32, 40 and 48 hour points) prior to time point. The 30 minutes of video-EEG did not need to be continuous. Absolute reduction in seizure burden for these time points was calculated as seizure burden in Baseline Period minus seizure burden at that time point.

Outcome measures

Outcome measures
Measure	Active Comparator n=6 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=11 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
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 Treatment, 7 hour - 8 hour	-2.74 mins/hour Standard Deviation 15.53	6.30 mins/hour Standard Deviation 6.74
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 Treatment, 15 hour - 16 hour	3.63 mins/hour Standard Deviation 5.28	7.21 mins/hour Standard Deviation 6.33
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 Treatment, 23 hour - 24 hour	5.08 mins/hour Standard Deviation 4.81	8.69 mins/hour Standard Deviation 8.06
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 Treatment, 31 hour - 32 hour	5.71 mins/hour Standard Deviation 5.09	8.93 mins/hour Standard Deviation 8.56
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 Treatment, 39 hour - 40 hour	4.43 mins/hour Standard Deviation 5.80	8.93 mins/hour Standard Deviation 8.56
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 Treatment, 47 hour - 48 hour	4.84 mins/hour Standard Deviation 5.44	8.93 mins/hour Standard Deviation 8.56

SECONDARY outcome

Timeframe: Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline

The percent change in seizure burden for the 8, 16, 24, 32, 40 and 48 hour time points was calculated as the seizure burden at Baseline minus the seizure burden at the respective time point, divided by the seizure burden in the Baseline Period, multiplied by 100. Percent change in seizure burden was analyzed such that a positive value indicates a reduction in seizure burden from baseline.

Outcome measures

Outcome measures
Measure	Active Comparator n=6 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=11 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
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 Treatment, 7 hour - 8 hour	39.85 percent change Standard Deviation 147.33	80.92 percent change Standard Deviation 45.56
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 Treatment, 15 hour - 16 hour	48.22 percent change Standard Deviation 116.94	93.19 percent change Standard Deviation 21.53
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 Treatment, 23 hour - 24 hour	100.00 percent change Standard Deviation 0.00	99.03 percent change Standard Deviation 3.05
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 Treatment, 31 hour - 32 hour	100.00 percent change Standard Deviation 0.00	100.00 percent change Standard Deviation 0.00
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 Treatment, 39 hour - 40 hour	77.13 percent change Standard Deviation 45.73	100.00 percent change Standard Deviation 0.00
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 Treatment, 47 hour - 48 hour	100.00 percent change Standard Deviation 0.00	100.00 percent change Standard Deviation 0.00

SECONDARY outcome

Timeframe: Across the first 48 hours of Treatment Period

Population: The FAS consisted of all study participants in the SS who had a minimum of 30 minutes of interpretable video-EEG data from both Baseline and the period between 1 and 3 hours (Evaluation Period) after randomization to the initial study medication treatment. FAS population was based on randomized treatment. Here, overall number of participants analyzed included all participants who were evaluable for this assessment.

A responder is defined as a study participant who achieved the following reduction in seizure burden without need for rescue medication, compared with the seizure burden measured during the Baseline Period immediately prior to investigational medicinal product (IMP) administration, evaluated for a 2-hour period starting 1 hour after the start of initial treatment: At least 80% reduction of seizure burden in participants who were categorized as having nonsevere seizure burden during Baseline OR At least 50% reduction of seizure burden in participants who had at least one 30-minute period of severe seizure burden during Baseline. The denominator for the percentages was based on the number of participants with video- EEG data available at the 48 hour time point.

Outcome measures

Outcome measures
Measure	Active Comparator n=6 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=13 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Percentage of Responders at the End of the First 48-hours of the Treatment Period	66.7 percentage of participants	76.9 percentage of participants

SECONDARY outcome

Timeframe: 24 hours after the start of Treatment Period, compared to Baseline

Population: FAS consisted of all study participants in the SS who had minimum of 30 minutes of interpretable video-EEG data from both Baseline and period between 1 and 3 hours (Evaluation Period) after randomization to initial study medication treatment. FAS population was based on randomized treatment. Here, "N"=participants who were evaluable for this assessment and "n"= participants who were evaluable for specified seizure burden categories.

Seizure free was defined as 100% reduction in seizure burden or having no seizures in the assessment period (23 to 24 hours after first dose) from Baseline. For the study participants with severe seizure burden at Baseline (as determined by the Investigator), the numerator was defined as the number of participants with severe seizure burden at Baseline who had no seizures between 23 and 24 hours after the start of the Treatment Period. The denominator for the percentages was based on the number of participants with video-EEG data available at the 24 hour time point. Here, N='overall number of participants analyzed' and n='number analyzed' in categories.

Outcome measures

Outcome measures
Measure	Active Comparator n=8 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=14 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
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 Non Severe or Severe Seizure Burden at Baseline Severe Seizure Burden	33.3 percentage of participants	66.7 percentage of participants
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 Non Severe or Severe Seizure Burden at Baseline Non-severe Seizure Burden	100.0 percentage of participants	62.5 percentage of participants

SECONDARY outcome

Timeframe: During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline

Population: FAS consisted of all study participants in the SS who had minimum of 30 minutes of interpretable video-EEG data from both Baseline and period between 1 and 3 hours (Evaluation Period) after randomization to the initial study medication treatment. FAS population was based on randomized treatment. Here, overall number of participants analyzed included all participants who were evaluable for this assessment.

Baseline seizure burden was calculated as total duration of seizures (in minutes) between -2 and 0 hours before the first dose of study medication divided by total duration of interpretable video-EEG (in hours) in same period. Seizure burden in Evaluation Period was calculated as total duration of seizures between 1 and 3 hours after first dose of study medication divided by duration of interpretable video-EEG available in same period. Percent change in seizure burden for Evaluation period was calculated as seizure burden at Baseline minus seizure burden at respective time point, divided by seizure burden in Baseline Period, multiplied by 100. Participants classified in one of following categories based on their percent reduction from Baseline to Evaluation Period: \< -25% (worsening), -25% to \<25% (no change), 25% to \<50%, 50% to \<80%, and \>=80%. Percent change in seizure burden was analyzed and categorized such that positive value indicates reduction in seizure burden from baseline.

Outcome measures

Outcome measures
Measure	Active Comparator n=9 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=11 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG Evaluation, 1 hour - 3 hour: 50% to <80%	22.2 Percentage of participants	0.0 Percentage of participants
Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG Evaluation, 1 hour - 3 hour: <-25%	22.2 Percentage of participants	0.0 Percentage of participants
Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG Evaluation, 1 hour - 3 hour: -25% to <25%	0.0 Percentage of participants	9.1 Percentage of participants
Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG Evaluation, 1 hour - 3 hour: 25% to <50%	11.1 Percentage of participants	9.1 Percentage of participants
Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG Evaluation, 1 hour - 3 hour: >=80%	44.4 Percentage of participants	81.8 Percentage of participants

SECONDARY outcome

Timeframe: From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42)

Population: The SS consisted of all enrolled study participants who took at least 1 dose of the randomized treatment. The safety population was based on actual treatment.

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. TEAEs are defined as AEs which have onset on or after the start date and time of initial study medication administration.

Outcome measures

Outcome measures
Measure	Active Comparator n=12 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=14 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) as Reported by the Investigator	41.7 percentage of participants	64.3 percentage of participants

SECONDARY outcome

Timeframe: Active Comparator: Screening; Lacosamide: Screening, 1-6 hours, 48 and 96 hours

Population: The SS consisted of all enrolled study participants who took at least 1 dose of the randomized treatment. The safety population was based on actual treatment. Here, overall number of participants analyzed included all participants with a non-missing interpretation for this assessment and number analyzed signifies participants who were evaluable at specified timepoints.

The ECG treatment-emergent marked abnormalities values are based on grade 2 toxicity based on abnormal values or clinical experience based on investigator's discretion. Participants randomized to Lacosamide and enrolled under this version of the protocol have planned assessments at Screening, 1-6 hours, 48, and 96 hours only. For participants randomized to Active Comparator treatment, only the Screening assessment was applicable.

Outcome measures

Outcome measures
Measure	Active Comparator n=8 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=14 Participants Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Percentage of Participants With Treatment-emergent Marked Abnormalities in 12-lead Electrocardiogram (ECG) Screening: Abnormal Clinically significant	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Treatment-emergent Marked Abnormalities in 12-lead Electrocardiogram (ECG) 1-6 hours: Abnormal Clinically significant	—	0.0 percentage of participants
Percentage of Participants With Treatment-emergent Marked Abnormalities in 12-lead Electrocardiogram (ECG) 48 hours: Abnormal Clinically significant	—	0.0 percentage of participants
Percentage of Participants With Treatment-emergent Marked Abnormalities in 12-lead Electrocardiogram (ECG) 96 hours: Abnormal Clinically significant	—	0.0 percentage of participants

SECONDARY outcome

Timeframe: Day 1: 30-90 minutes and 6 - 8 hours after start of first infusion, 30 - 90 minutes and 6 - 8 hours after start of second or third infusion, Days 2, 3 and 4

Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all study participants who provide at least 1 measurable serum sample (with recorded sampling time) on at least 1 post-Baseline visit with documented study drug intake times. Here, overall number of participants analyzed included all participants who were evaluable for this assessment and number analyzed signifies participants who were evaluable at specified timepoints.

Serum concentrations of lacosamide were measured and concentration data were summarized. PK sparse sampling was performed.

Outcome measures

Outcome measures
Measure	Active Comparator n=13 Participants Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Serum Concentration of Lacosamide Day 2	NA microgram per milliliter (mcg/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric Coefficient of Variation could not be calculated for a single participant.	—
Serum Concentration of Lacosamide Day 3	NA microgram per milliliter (mcg/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric Coefficient of Variation could not be calculated for less than 3 participants.	—
Serum Concentration of Lacosamide Day 4	NA microgram per milliliter (mcg/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric Coefficient of Variation could not be calculated for less than 3 participants.	—
Serum Concentration of Lacosamide Day 1: 30 - 90 minutes after start of first infusion	7.003 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 37.6	—
Serum Concentration of Lacosamide Day 1: 6 - 8 hours after start of first infusion	5.949 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 38.6	—
Serum Concentration of Lacosamide Day 1: 30 - 90 minutes after start of second or third infusion	13.27 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 29.4	—
Serum Concentration of Lacosamide Day 1: 6 - 8 hours after start of second or third infusion	9.607 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 39.8	—

Adverse Events

No Treatment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Active Comparator

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Lacosamide

Serious events: 2 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	No Treatment n=3 participants at risk Participant signed the informed consent form, successfully screened and randomized but never received any study medication during the study.	Active Comparator n=12 participants at risk Study participants randomized to receive Active Comparator (chosen and dosed based on standard of care (StOC) per local practice and treatment guidelines) in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized Active Comparator in the Extension Period (up to 28 days of postnatal age). Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day Safety Follow-up (SFU) Period with optional down titration.	Lacosamide n=14 participants at risk Study participants randomized to receive lacosamide 10 milligram per milliliter (mg/mL) 3 times a day as an intravenous infusion over 30 minutes for up to 96 hours in the Treatment Period. After the Treatment Period, study participants had the option to continue to receive randomized lacosamide in the Extension Period (up to 28 days of postnatal age), being switched to oral dosing of lacosamide as soon as medically possible. Study participants (whether they discontinued randomized treatment during the Treatment Period, completed the Extension Period, were discharged from the hospital, or reached 28 days of postnatal age) then entered the 14-day SFU Period with optional down titration.
Congenital, familial and genetic disorders Congenital central nervous system anomaly	0.00% 0/3 • Enrolment: Screening (-36 hours) up to 0 hours (pre-dose); Treatment: From first administration of study treatment to the End of Safety Follow-up (up to Day 42) TEAEs are defined as AEs which had onset on or after the start date and time of initial study medication administration. The SS consisted of all enrolled study participants who took at least 1 dose of the randomized treatment. Eligible participants who did not undergo any treatment of lacosamide but experienced an AE, are presented in a separate group "No Treatment".	0.00% 0/12 • Enrolment: Screening (-36 hours) up to 0 hours (pre-dose); Treatment: From first administration of study treatment to the End of Safety Follow-up (up to Day 42) TEAEs are defined as AEs which had onset on or after the start date and time of initial study medication administration. The SS consisted of all enrolled study participants who took at least 1 dose of the randomized treatment. Eligible participants who did not undergo any treatment of lacosamide but experienced an AE, are presented in a separate group "No Treatment".	7.1% 1/14 • Number of events 1 • Enrolment: Screening (-36 hours) up to 0 hours (pre-dose); Treatment: From first administration of study treatment to the End of Safety Follow-up (up to Day 42) TEAEs are defined as AEs which had onset on or after the start date and time of initial study medication administration. The SS consisted of all enrolled study participants who took at least 1 dose of the randomized treatment. Eligible participants who did not undergo any treatment of lacosamide but experienced an AE, are presented in a separate group "No Treatment".
Nervous system disorders Cerebral infarction	0.00% 0/3 • Enrolment: Screening (-36 hours) up to 0 hours (pre-dose); Treatment: From first administration of study treatment to the End of Safety Follow-up (up to Day 42) TEAEs are defined as AEs which had onset on or after the start date and time of initial study medication administration. The SS consisted of all enrolled study participants who took at least 1 dose of the randomized treatment. Eligible participants who did not undergo any treatment of lacosamide but experienced an AE, are presented in a separate group "No Treatment".	0.00% 0/12 • Enrolment: Screening (-36 hours) up to 0 hours (pre-dose); Treatment: From first administration of study treatment to the End of Safety Follow-up (up to Day 42) TEAEs are defined as AEs which had onset on or after the start date and time of initial study medication administration. The SS consisted of all enrolled study participants who took at least 1 dose of the randomized treatment. Eligible participants who did not undergo any treatment of lacosamide but experienced an AE, are presented in a separate group "No Treatment".	7.1% 1/14 • Number of events 1 • Enrolment: Screening (-36 hours) up to 0 hours (pre-dose); Treatment: From first administration of study treatment to the End of Safety Follow-up (up to Day 42) TEAEs are defined as AEs which had onset on or after the start date and time of initial study medication administration. The SS consisted of all enrolled study participants who took at least 1 dose of the randomized treatment. Eligible participants who did not undergo any treatment of lacosamide but experienced an AE, are presented in a separate group "No Treatment".

Other adverse events

Additional Information

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Principal investigator is a sponsor employee
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Restriction type: GT60