Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001066-10 | EudraCT Number |
Not provided
Not provided
Study stopped after agreed PIP modification, not linked to safety reasons.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of the study is to 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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lacosamide | Experimental | Study participants randomized to this arm will receive lacosamide (LCM) as an intravenous infusion in the Treatment Period and may continue to receive lacosamide in the Extension Period. Participants should be switched to oral dosing of LCM as soon as medically possible during the Extension Period. |
|
| Active Comparator | Active Comparator | Study participants randomized to this arm will receive Active Comparator chosen based on standard of care (StOC) in the Clinical Practice in the Treatment Period and may continue to receive in the Extension Period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lacosamide intravenous | Drug | Study participants will receive lacosamide (LCM) as an intravenous (iv) infusion during the Treatment Period. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Seizure Burden Measured in the Evaluation Video-electroencephalogram (Video-EEG) Compared With the Baseline Video-EEG | 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. | During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Responders in the Evaluation Video-EEG Compared With the Baseline Video-EEG | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| UCB Cares | 001 844 599 2273 | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sp0968 101 | La Jolla | California | 92037 | United States | ||
| Sp0968 108 |
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed.All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
The Participant Flow refers to the Safety set. This study was ended after agreed Pediatric investigation plan (PIP) modification, not linked to safety reasons.
The study started to enrol participants in March 2021 and concluded in October 2024.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | No Treatment | Participant signed the informed consent form, successfully screened and randomized but never received any study medication during the study. |
| FG001 | Active Comparator |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Enrollment Period (Up to 36 Hours) |
|
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 11, 2022 | Aug 5, 2025 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Lacosamide oral | Drug | Study participants may receive lacosamide (LCM) as an oral solution during the Extension Period. |
|
|
| Active Comparator | Other | Active Comparator treatment will be chosen and dosed based on StOC (per local practice and treatment guidelines). |
|
| During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline |
| Percentage of Participants With at Least 80% Reduction in Seizure Burden in the Evaluation a Video-EEG Compared With the Baseline Video-EEG | 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. | During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline |
| Time to Response Across the 48-hour Treatment Period Compared With the Baseline Video-EEG | 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. | Across the first 48 hours of Treatment Period, compared to Baseline |
| Time to Seizure Freedom Across the First 48-hour Treatment Period Compared With the Baseline Video-EEG | 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. | Across the first 48 hours of Treatment Period, compared to Baseline |
| 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 | 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. | Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline |
| 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 | 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. | Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline |
| Percentage of Responders at the End of the First 48-hours of the Treatment Period | 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. | Across the first 48 hours of Treatment Period |
| 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 | 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. | 24 hours after the start of Treatment Period, compared to Baseline |
| Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG | 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. | During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) as Reported by the Investigator | 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. | From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42) |
| Percentage of Participants With Treatment-emergent Marked Abnormalities in 12-lead Electrocardiogram (ECG) | 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. | Active Comparator: Screening; Lacosamide: Screening, 1-6 hours, 48 and 96 hours |
| Serum Concentration of Lacosamide | Serum concentrations of lacosamide were measured and concentration data were summarized. PK sparse sampling was performed. | 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 |
| Long Beach |
| California |
| 90806 |
| United States |
| Sp0968 116 | Los Angeles | California | 90095 | United States |
| Sp0968 190 | San Diego | California | 92123 | United States |
| Sp0968 118 | Aurora | Colorado | 80045 | United States |
| Sp0968 104 | Jacksonville | Florida | 32207 | United States |
| Sp0968 107 | Miami | Florida | 33155 | United States |
| Sp0968 112 | Iowa City | Iowa | 52242 | United States |
| Sp0968 125 | Valhalla | New York | 10595 | United States |
| Sp0968 117 | Portland | Oregon | 97239 | United States |
| Sp0968 109 | Austin | Texas | 78723 | United States |
| Sp0968 192 | Salt Lake City | Utah | 84113 | United States |
| Sp0968 105 | Salt Lake City | Utah | 84132 | United States |
| Sp0968 102 | Charlottesville | Virginia | 22903 | United States |
| Sp0968 122 | Seattle | Washington | 98105 | United States |
| Sp0968 302 | Parkville | Australia |
| Sp0968 301 | South Brisbane | Australia |
| Sp0968 201 | Toronto | Canada |
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.
| FG002 | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Treatment Period (Up to 96 Hours) |
|
|
| Extension Period: up to 28 Days of PNA |
|
| Safety Follow Up Period: 14 Days |
|
The Safety Set (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. As pre-defined in the SAP, Baseline data was collected and reported for Treated population only.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | days |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Seizure Burden Measured in the Evaluation Video-electroencephalogram (Video-EEG) Compared With the Baseline Video-EEG | 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. | 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. | Posted | Mean | Standard Deviation | minute per hour (min/hour) | During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline |
|
|
| ||||||||||||||||||||||||||||
| Secondary | Percentage of Responders in the Evaluation Video-EEG Compared With the Baseline Video-EEG | 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. | 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. | Posted | Number | percentage of participants | During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline |
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With at Least 80% Reduction in Seizure Burden in the Evaluation a Video-EEG Compared With the Baseline Video-EEG | 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. | 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. | Posted | Number | percentage of participants | During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline |
| |||||||||||||||||||||||||||||||
| Secondary | Time to Response Across the 48-hour Treatment Period Compared With the Baseline Video-EEG | 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. | 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. | Posted | Median | 95% Confidence Interval | hours | Across the first 48 hours of Treatment Period, compared to Baseline |
| ||||||||||||||||||||||||||||||
| Secondary | Time to Seizure Freedom Across the First 48-hour Treatment Period Compared With the Baseline Video-EEG | 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. | 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. | Posted | Median | 95% Confidence Interval | hours | Across the first 48 hours of Treatment Period, compared to Baseline |
| ||||||||||||||||||||||||||||||
| Secondary | 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 | 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. | 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. | Posted | Mean | Standard Deviation | mins/hour | Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline |
| ||||||||||||||||||||||||||||||
| Secondary | 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 | 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. | 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. | Posted | Mean | Standard Deviation | percent change | Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline |
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Responders at the End of the First 48-hours of the Treatment Period | 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. | 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. | Posted | Number | percentage of participants | Across the first 48 hours of Treatment Period |
| |||||||||||||||||||||||||||||||
| Secondary | 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 | 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. | 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. | Posted | Number | percentage of participants | 24 hours after the start of Treatment Period, compared to Baseline |
| |||||||||||||||||||||||||||||||
| Secondary | Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG | 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. | 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. | Posted | Number | Percentage of participants | During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline |
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) as Reported by the Investigator | 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. | 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. | Posted | Number | percentage of participants | From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42) |
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Treatment-emergent Marked Abnormalities in 12-lead Electrocardiogram (ECG) | 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. | 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. | Posted | Number | percentage of participants | Active Comparator: Screening; Lacosamide: Screening, 1-6 hours, 48 and 96 hours |
| |||||||||||||||||||||||||||||||
| Secondary | Serum Concentration of Lacosamide | Serum concentrations of lacosamide were measured and concentration data were summarized. PK sparse sampling was performed. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram per milliliter (mcg/mL) | 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 |
|
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".
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | No Treatment | Participant signed the informed consent form, successfully screened and randomized but never received any study medication during the study. | 0 | 3 | 0 | 3 | 1 | 3 |
| EG001 | 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. | 0 | 12 | 0 | 12 | 5 | 12 |
| EG002 | 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. | 1 | 14 | 2 | 14 | 8 | 14 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Congenital central nervous system anomaly | Congenital, familial and genetic disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Right ventricular hypertrophy | Cardiac disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Adrenal haemorrhage | Endocrine disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Diabetes insipidus | Endocrine disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Retinal haemorrhage | Eye disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia neonatal | Hepatobiliary disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Neonatal infection | Infections and infestations | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Feeding disorder neonatal | Metabolism and nutrition disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Poor sucking reflex | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Reflexes abnormal | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Cerebrospinal fluid leakage | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Depressed level of consciousness | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Intracranial pressure increased | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Hypercapnia | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 16.1 | Non-systematic Assessment |
| |
| Elevated Alanine Aminotransferase | Investigations | MedDRA version 16.1 | Non-systematic Assessment |
|
The study ended prematurely after agreed PIP modification; the termination was not linked to any safety issues/reasons.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| UCB | Cares | +1-844-599-2273 | UCBCares@ucb.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 4, 2023 | Aug 5, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000078334 | Lacosamide |
| ID | Term |
|---|---|
| D000081 | Acetamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| White |
|
| Other or Mixed |
|
| Missing |
|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
| 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. |
|
|
| OG001 | 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. |
|
|
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. |
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
| OG001 | 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. |
|
|
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.
| OG001 | 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. |
|
|
|
|
| OG001 | 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. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|