Principal Investigator: Mariana  Baserga
Keywords: Neonates , electroencephalographic neonatal seizures , Lacosamide Department: Pediatric Administration
IRB Number: 00135323
Specialty: Neonatology, Neurology
Sub Specialties: Seizures
Recruitment Status: Recruiting

Contact Information

Carrie Rau
Carrie.Rau@hsc.utah.edu
801-581-2746

Brief Summary

Primary Objective: To evaluate the efficacy of Lacosamide (LCM) vs an Active Comparator chosen based on local 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 AED treatment

Secondary Objectives: 

To further evaluate the efficacy of LCM vs an Active Comparator in severe and nonsevere seizure burden (defined as total minutes of ENS per hour) in neonates with seizures that are not adequately controlled with previous AED treatment through review of video EEG

To evaluate the short-term safety and tolerability of LCM in neonates

To evaluate the PK of LCM in neonates who have seizures that are not adequately controlled with previous AED treatment

Inclusion Criteria

Age

1. Participant must be at least 34 weeks of GA. In addition, term neonates up to 28 days of postnatal age and preterm neonates up to 40 weeks of postmenstrual age and 28 days of postnatal age can be enrolled, at the time of signing the informed consent.

 

Type of participant and disease characteristics

2. Participants who have confirmation on video-EEG of ≥2 minutes of cumulative ENS or ≥3 identifiable ENS prior to entering the Treatment Period (ENS is defined as a seizure lasting for at least 10 seconds on video-EEG), despite receiving previous AED treatment for the treatment of electroencephalographic seizures.

The occurrence of ENS during an up to 1-hour period must be confirmed by the local video-EEG reader prior to randomized study drug administration. Video-EEG recording can be shortened per clinical need (eg, if status epilepticus is detected). If possible, an attempt should be made to record at least 30 minutes of Baseline video-EEG.

3. Participants must have received either PB, LEV, or MDZ (in any combination) before entering the study.

4. Participants with or without concomitant hypothermia treatment.

 

Weight

5. Participant weighs at least 2.3kg at the time of enrollment.

 

Informed consent

6. An Independent Ethics Committee (IEC)-approved written ICF is signed and dated by the participant’s parent(s) or legal representative(s).

Exclusion Criteria

Medical conditions

1. Participant with seizures responding to correction of metabolic disturbances or with seizures for which a targeted, known treatment is available.

2. Participant has seizures related to prenatal maternal drug use or drug withdrawal.

3. Participant has known severe disturbance of hemostasis, as assessed by the investigator.

4. Participant has a poor prognosis for survival, as judged by the investigator.

5. Participant has a medical condition that could be expected, in the opinion of the investigator, to interfere with study medication absorption, distribution, metabolism, or excretion.

6. Participant has a clinically relevant ECG abnormality, in the opinion of the investigator (eg, second or third degree heart block at rest or a corrected QT interval [QTc] ≥450ms).

7. Participant has a hemodynamically significant congenital heart disease.

8. Participant has any clinically relevant cardiac arrhythmia.

9. Participant has creatinine clearance <30mL/minute, as approximated by estimated glomerular
filtration rate using the revised Schwartz formula.

 

Prior/Concomitant therapy

10. Participant receiving treatment with PHT, LDC, or other sodium channel blockers at any time.

11. Participant requires extracorporeal membrane oxygenation.

12. Participant requires or is expected to require phototherapy or exchange transfusion due to elevated bilirubin.

 

Diagnostic assessments

13. Participant has 2x upper limit of normal (ULN) of any of the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), with the following exception:

For participants with perinatal asphyxia, elevation of AST, ALT, or ALP <5x ULN is acceptable, if initial and peak elevation of liver function tests (LFTs) occur within 5 days after birth, and the time course of LFT elevation is compatible with hepatic injury due to perinatal asphyxia. The determination of ULN will be based on the participant's gestationally-corrected age (GCA) and the site’s normal range values for the respective GCA.

14. Participant has direct (conjugated) bilirubin levels >2mg/dL.