refractory epilepsy with partial-onset seizures in children aged from 1 month to < 2 years MedDRA version: 21.1 Level: LLT Classification code 10065336 Term: Partial epilepsy System Organ Class: 100000004852
Conditions
Sponsors
BIAL - Portela & Ca, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have an informed consent signed by their parent(s) or guardian(s) before undergoing any study-related activities. 2. Male or female =1 month (i.e. at least 28 days) but =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. A neonate who is a preterm baby (i.e. born before 36 weeks of gestation). 2. Diagnosis of treatable seizure aetiology such as metabolic, toxic, and infectious disorders. 3. Primarily generalised seizures. 4. Known rapidly progressive neurological disorders (e.g. rapidly progressive brain disease, epilepsy secondary to rapidly progressive cerebral lesion). 5. History of status epilepticus or cluster seizures (i.e. 3 or more seizures within 30 minutes) within the month prior to screening. 6. Seizures of non-epileptic origin. Ohtahara syndrome, West syndrome [current], Dravet’s syndrome, or Lennox-Gastaut syndrome). 8. Difficult venous access. 9. Ketogenic diet. 10. Currently treated with OXC (at Screening or for at least 2 weeks before). 11. Previous use of ESL. 12. An AED that started or was discontinued in the 3 weeks before Visit 1. 13. Diseases that can have an impact on drug absorption (e.g. any disease leading to diarrhoea or vomiting). 14. Treatments that can have an impact on blood volume (e.g. transfusions or intravenous infusions). 15. Hypersensitivity to the active substance, to other carboxamide derivatives (e.g. carbamazepine, OXC), or to any of the excipients, in particular methyl parahydroxybenzoate (E218) or sulphites. 16. Uncontrolled cardiac (including atrioventricular block and other clinically significant electrocardiographic abnormalities), renal, hepatic, endocrine, gastrointestinal, metabolic, haematological, or oncology disorders. 17. Relevant clinical laboratory abnormalities (e.g. sodium 2 x the upper limit of normal, white blood cell count <3000 cells/mm3) (measured at Visit 1). 18. Estimated glomerular filtration rate below the lower limit of the normal range (measured at Visit 1). 19. Participation in other drug clinical trial within the last 2 months or having received an IMP within 5 half-lives of that IMP, whichever is longer. 20. Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject’s ability to comply with the study protocol. 21. Known presence of HLA-A*3101 allele.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the steady state PK profile of ESL.;Secondary Objective: To assess the safety and tolerability of ESL in the defined patient population at the doses used and to perform exploratory analyses of efficacy.;Primary end point(s): • Minimum (i.e. pre-dose) plasma concentration (Cmin). • Maximum observed plasma concentration (Cmax). • Time of occurrence of Cmax (tmax). • Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t), calculated by the linear trapezoidal rule. • AUC from time zero to 24 hours post-dose (AUC0-t). • Apparent terminal rate constant (?z) calculated by log-linear regression of the terminal segment of the drug plasma concentration versus time curve. • Apparent half-life (t1/2), calculated from ln 2/?z. • Apparent plasma clearance (CL/F), calculated from Dose/AUC0-t. Additional PK parameters may also be calculated if considered appropriate. ;Timepoint(s) of evaluation of this end point: • An interim analysis of the PK data will be performed after at least 8 subjects in Group 1 (4 in each age group) have completed their 24-hour PK profile. • At the end of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • Seizures (date, time, type, and duration) recorded by the investigator at each visit. Safety: • Treatment-emergent adverse events (TEAEs) defined as all AEs with onset or worsening after first intake of study treatment until 4 weeks after last intake of study treatment. • Clinical laboratory safety tests: - Biochemistry: sodium, potassium, calcium, creatinine, blood urea nitrogen, aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, albumin, total protein, total bilirubin, and glucose. - Haematology: haemoglobin, haematocrit, erythrocyte count, leucocyte count with differential, and platelet count. • Urinalysis: local dipstick test of pH, specific gravity, protein, blood, glucose, ketones, bilirubin, and urobilinogen. If dipstick results indicate a significant abnormality, microscopy and other appropriate tests (as needed) will be performed by the central laboratory. • Physical examination, vital signs, neurological examination, and electrocardiogram. ;Timepoint(s) of evaluation of this end point: At the end of the trial | — |
Countries
Croatia, Czech Republic, Italy, Portugal, Romania, Russian Federation, Serbia, Ukraine
Contacts
Public ContactSponsor
BIAL - Portela & Ca, S.A.
Outcome results
None listed