A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures
- Conditions
- Electroencephalographic Neonatal SeizuresEpilepsy
- Interventions
- Registration Number
- NCT04519645
- Lead Sponsor
- UCB Biopharma SRL
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 29
- Participant must be ≥34 weeks of corrected gestational age (CGA), <46 weeks of CGA, and <28 days of postnatal age (PNA)
- Participants who have confirmation on video-electroencephalogram (EEG) of ≥2 minutes of cumulative electroencephalographic neonatal seizures (ENS) or ≥3 identifiable ENS prior to entering the Treatment Period
- Participants must have received either phenobarbital (PB), levetiracetam (LEV), or midazolam (MDZ) (in any combination) before entering the study
- Participant weighs at least 2.3 kg at the time of enrollment Informed consent
- An Independent Ethics Committee (IEC)-approved written informed consent form (ICF) is signed and dated by the participant's parent(s) or legal representative(s)
- Participant with seizures responding to correction of metabolic disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia) or with seizures for which a targeted, known treatment is available
- Participant has seizures related to prenatal maternal drug use or drug withdrawal
- Participant has a clinically relevant electrocardiogram (ECG) abnormality, in the opinion of the investigator
- Participant receiving treatment with phenytoin (PHT), lidocaine (LDC), or other sodium channel blockers at any time
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lacosamide Lacosamide intravenous 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. Lacosamide Lacosamide oral 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.
- Primary Outcome Measures
Name Time Method Change in seizure burden measured in the Evaluation video-electroencephalogram (video-EEG) compared with the Baseline video-EEG During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours) Change in seizure burden measured in the Evaluation video-EEG compared with the Baseline video-EEG.
Baseline seizure burden is 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.
- Secondary Outcome Measures
Name Time Method Categorized percentage change in seizure burden in the Evaluation video-EEG compared with the Baseline video-EEG During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours) The change in seizure burden will be presented in the following categories: (\<-25% \[worsening\], -25% to \<25% \[no change\], 25% to \<50%, 50% to \<80%, and ≥80%)
Percentage of participants with at least 80% reduction in seizure burden in the Evaluation a video-EEG compared with the Baseline video-EEG During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours) 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 BaselineTime to response across the 96-hour Treatment Period Across the Treatment Period (up to 96 hours) Time to response is presented as median time (in hours) to the 50% reduction in study participants with severe seizure burden or 80% reduction in study participants with nonsevere seizure burden.
Percentage of participants with treatment-emergent marked abnormalities in 12-lead electrocardiogram (ECG) From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42) Marked abnormalities are defined as abnormalities in predefined parameters based upon grade 2 toxicity lab values and neonatologist expert opinion in the neonate.
Time to seizure freedom across the 96-hour Treatment Period Across the Treatment Period (up to 96 hours) Time to seizure freedom will be analyzed as median time (in hours) to seizure freedom.
Percentage of participants with treatment-emergent adverse events (TEAEs) as reported by the investigator From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42) 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.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.Percentage of responders in the Evaluation video-EEG compared with the Baseline video-EEG During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours) 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 BaselinePlasma/serum concentration of lacosamide (LCM) Across the Treatment Period (up to 96 hours) Mean plasm/serum concentrations of lacosamide (LCM) will be presented across the Treatment Period.
Trial Locations
- Locations (18)
Sp0968 118
🇺🇸Aurora, Colorado, United States
Sp0968 101
🇺🇸La Jolla, California, United States
Sp0968 108
🇺🇸Long Beach, California, United States
Sp0968 116
🇺🇸Los Angeles, California, United States
Sp0968 190
🇺🇸San Diego, California, United States
Sp0968 104
🇺🇸Jacksonville, Florida, United States
Sp0968 107
🇺🇸Miami, Florida, United States
Sp0968 112
🇺🇸Iowa City, Iowa, United States
Sp0968 125
🇺🇸Valhalla, New York, United States
Sp0968 117
🇺🇸Portland, Oregon, United States
Sp0968 109
🇺🇸Austin, Texas, United States
Sp0968 192
🇺🇸Salt Lake City, Utah, United States
Sp0968 105
🇺🇸Salt Lake City, Utah, United States
Sp0968 102
🇺🇸Charlottesville, Virginia, United States
Sp0968 122
🇺🇸Seattle, Washington, United States
Sp0968 302
🇦🇺Parkville, Australia
Sp0968 301
🇦🇺South Brisbane, Australia
Sp0968 201
🇨🇦Toronto, Canada