Dose-Escalation Study of Cenobamate (YKP3089) in Pediatric Subjects With Partial-Onset Seizures

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sk Life Science Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

26 Feb 2025 → 6 Nov 2025

Decision date (initial)

2025-01-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

SK Life Science, Inc.

External identifiers

EU CT number

2024-514045-11-00

ClinicalTrials.gov

NCT04903314

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Dose response, Pharmacokinetic, Others

The primary objective of this study is to assess the pharmacokinetics of cenobamate (YKP3089)
in pediatric subjects (ages 2 to less than 18) with partial-onset (focal) seizures following single
and multiple-dosing.

Secondary objectives 1

1. The secondary objective of this study is to evaluate the safety and tolerability of cenobamate (YKP3089) following single and multiple dosing.

Conditions and MedDRA coding

Partial Onset Seizures

Study design 4 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002563-PIP02-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Diagnosis of epilepsy with partial-onset seizures (POS) with or without secondarily generalized seizures according to the International League Against Epilepsy’s (ILAE) Classification of Epileptic Seizures. A diagnosis should have been established at least 6 months prior to Study Day 1 by clinical history and an electroencephalogram (EEG) that is consistent with the diagnosis; normal interictal EEGs will be allowed provided that the participant meets the other diagnosis criterion (i.e., clinical history, including a history of treatment failure with at least 2 AEDs)
2. Male or female subject, from age 2 to less than 18 years at the time of informed consent
3. Minimum and maximum weights for cohorts IIa, IIb and III are as follows (Males and Females, 3-97 Percentile (i.e., Min-Max), Body Weight, kg). This will capture 94% of the weights of boys and girls of each age group to obtain an accurate estimate for dosing: a. cohort IIa - 16-63 kg b. cohort IIb - 13-28 kg c. cohort III - 10-20 kg
4. Written informed consent signed by the subject, legal guardian, or legally authorized representative (LAR) prior to entering the study in accordance with the ICH GCP guidelines. Age-appropriate assent will be obtained for children and adolescents when the subject is cognitively able.
5. Are currently being treated with stable doses of 1 to a maximum of 3 approved antiepileptic drugs (AEDs). Doses must be stable for at least 4 weeks before Study Day 1; A vagal nerve stimulator (VNS) will not be counted as one of the 3 allowable AEDs
6. In the Investigator’s opinion, parents or caregivers must be able to report accurate seizure assessments during the screening and study periods and subjects must be able to ingest study drug
7. Subjects with an implanted vagal nerve stimulator will be allowed if the vagal nerve stimulator was implanted at least 5 months prior to Screening and the stimulator parameters have not been changed for 30 days prior to Screening.
8. Subjects following a ketogenic diet will be allowed as long as the diet has been stable for at least 30 days prior to Screening and will remain stable for the duration of the study

Exclusion criteria 31

1. Progressive neurological disease, including degenerative CNS diseases and progressive tumors
2. Evidence of clinically significant disease or any medical condition that would compromise the subject’s ability to safely complete the study including, but not limited to, hepatic or renal failure, ischemic disease, human immunodeficiency virus (HIV) infection, active sexually transmitted disease (STD), active viral hepatitis, or malignancy
3. Positive urine screen of drugs of abuse (if not due to concomitant medication, e.g., benzodiazepines as hypnotics) for Cohort 1 subjects.
4. History of anoxic episodes require resuscitation within 6 months before the Screening Visit, drug or alcohol dependency or abuse within approximately the last 2 years or use of illegal recreational drugs.
5. Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational product
6. Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or soda) or alcoholic beverages within 72 hours before Day 1 and 72 hours before the day of multiple dose PK sampling (Day 59 for Cohort I)
7. Consumption of grapefruit or grapefruit-containing products within 72 hours before Day 1 and 72 hours before the day of multiple dose PK sampling (Day 59 for Cohort I)
8. Significant clinical laboratory abnormalities, including elevation of serum AST or ALT more than 2 times the upper limit or normal (ULN) for each age group.
9. Acute disease state (e.g., nausea, vomiting, fever, or diarrhea) within 7 days before Day 1
10. Scheduled for surgery during the study
11. Ketogenic diet or vagal nerve stimulation that has undergone alteration within 30 days of the Screening visit.
12. Treatment with an investigational drug or device (other than VNS) ≤ 30 days before the Screening visit.
13. Females who are breastfeeding or pregnant at Screening or Baseline or who are of reproductive age and do not agree to be abstinent or to use highly effective methods of contraception.
14. Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 5 years before the Screening visit
15. Have a history of status epilepticus that required hospitalization during the 6 months before the Screening visit
16. Have an unstable psychiatric diagnosis that may confound participants’ ability to participate in the study or that may prevent completion of the protocol-specified tests (e.g., in the judgement of the investigator, pose an appreciable risk for suicide, including suicidal behavior and ideation within 6 months before the Screening visit, current psychotic disorder, acute mania)
17. Any suicidal ideation with intent or without a plan within 6 months before the Screening visit in participants aged 6 and above as determined by the CSSR-S, if able
18. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the participant’s safety or interfere with study assessments
19. Evidence of significant hematological disease; white blood cell (WBC) count equal or less than 2500/μL (2.50 1E+09/L) or an absolute neutrophil count equal or less than 1000/μL (1.00 1E+09/L)
20. Clinically significant electrocardiogram (ECG) abnormality, including prolonged corrected QT interval (QTc) defined as greater than 450 msec or shortened corrected QT interval (QTc) defined as less than 350 msec
21. Subject has a history or any serious drug-induced hypersensitivity reaction (including, but not limited to, Stevens Johnson syndrome, toxic epidermal necrolysis, or DRESS) or any drug-related rash requiring hospitalization.
22. History or AED-associated rash that involved conjunctiva or mucosae
23. History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication
24. Concomitant use of phenytoin and clobazam as these drugs may influence cenobamate plasma exposure. Subjects who took phenytoin or clobazam in the past must be off these drugs for at least 30 days prior to Study Day 1.
25. Concomitant use of vigabatrin. Participants who took vigabatrin in the past must be off vigabatrin for at least 5 months before Study Day 1 and with documentation showing no evidence of vigabatrin-associated clinically significant abnormality in a visual perimetry test
26. Concomitant use of felbamate, Subjects who took felbamate in the past must be off this drug for at least 30 days prior to Study Day 1.
27. Use of potent enzyme-modifying drugs, including inhibitors of CYP enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals) and inducers of CYP enzymes (such as glucocorticoids, phenytoin, rifampin and St John`s Wort) in the previous 30 days prior to Study Day 1 of this study
28. A history of intermittent use of rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period is considered a 1-time rescue) more than twice within the 30 days prior to the Screening Visit.
29. A VNS implanted less than 5 months before the Screening visit or changes in parameter less than 30 days before the Screening visit
30. Presence of Familial short QT syndrome or relevant replicated QTc interval (QTcF less than 340 msec or greater than 450 msec in males and greater than 470 msec in females) on electrocardiogram (ECG)
31. Previous exposure to cenobamate or sensitivity/allergy to components of the tablets or oral suspension.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pharmacokinetic assessment for cenobamate in plasma after a single dose 2. Pharmacokinetic assessment for cenobamate in plasma after multiple dosing

Secondary endpoints 2

1. Safety and Tolerability • Treatment-emergent Adverse events, including AEs of special interest • Concomitant medication reporting • Safety laboratory tests • Electrocardiogram • Vital signs • Physical and neurological examination including growth measurements • Acceptability and palatability assessment
2. Efficacy • Seizure frequency data as the exploratory assessment of efficacy will be collected via seizure diary

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sk Life Science Inc.

Sponsor organisation

Sk Life Science Inc.

Address

461 From Road Fl 5

City

Paramus

Postcode

07652-3524

Country

United States

Scientific contact point

Organisation

Sk Life Science Inc.

Contact name

Pranoti Pradhan

Public contact point

Organisation

Sk Life Science Inc.

Contact name

Pranoti Pradhan

Third parties 9

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications