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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03678753




Registration number
NCT03678753
Ethics application status
Date submitted
18/09/2018
Date registered
20/09/2018
Date last updated
5/04/2024

Titles & IDs
Public title
Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Cenobamate Adjunctive Therapy in Subjects With PGTC Seizures
Secondary ID [1] 0 0
YKP3089C025
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Generalized Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cenobamate
Treatment: Drugs - Placebo

Experimental: Cenobamate - Cenobamate 12.5 mg tablet once a day for two weeks, 25 mg tablet once a day for two weeks, 50 mg tablet once a day for two weeks, 100 mg tablets once a day for two weeks, 150 mg tablets once a day for two weeks and 200 mg tablets once a day for twelve weeks. Adolescents will follow the same every two week regimen and receive cenobamate as an oral suspension based on weight.

Placebo Comparator: Placebo - Matching placebo


Treatment: Drugs: Cenobamate
12.5 mg tablet, 25 mg tablet, 50 mg tablet, 100 mg tablets, 150 mg tablets, 200 mg tablets. Adolescents will follow the same every two week regimen and receive cenobamate as an oral suspension based on weight.

Treatment: Drugs: Placebo
Matching Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Seizure Diary
Timepoint [1] 0 0
28 Days

Eligibility
Key inclusion criteria
1. Subject is male or female and aged =12 years.

2. Written informed consent signed by the subject or legal guardian, or legally
authorized representative (LAR), prior to entering the study, in accordance with the
International Conference on Harmonisation (ICH) Good Clinical Practice (GCP)
guidelines. Age- appropriate assent will be obtained for adolescents. If the written
informed consent is provided by the legal guardian because the subject is unable to do
so, a written or verbal assent from the subject must also be obtained. As required by
country-specific regulations, only the subject may sign the Informed Consent Form
(ICF) in accordance with ICH guidelines.

3. Female subjects of childbearing potential are willing to use an acceptable form of
birth control

4. Subject has a clinical diagnosis of PGTC seizures (with or without other subtypes of
generalized seizures) in the setting of idiopathic generalized epilepsy.

5. Subject experiences at least 5 PGTC seizures in 12 weeks during the Pre-Randomization
Period.

6. Subject has had a routine electroencephalogram (EEG) within 5 years prior to Visit1
(Screening/Baseline) or during the Pre-Randomization Period with
electroencephalographic features consistent with idiopathic generalized epilepsy;
other concomitant anomalies must be explained by adequate past medical history.

7. Subject has undergone computed tomography (CT) or magnetic resonance imaging (MRI)
within 10 years prior to Visit 1 (Screening/Baseline) or during the Pre-Randomization
Period that ruled out a progressive cause of epilepsy.

8. Subject is currently receiving 1 to a maximum of 3 concomitant AEDs with fixed dosing
regimens for a minimum of 30 days prior to Visit 1 (Screening/Baseline).

1. Benzodiazepines (except diazepam, see
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criterion No.7) taken at least
once per week during the 30 days prior to Visit 1 (Screening/Baseline) for
epilepsy, anxiety, or sleep disorder will be counted as 1 AED and the dosage must
be continued unchanged throughout the study. Therefore, only a maximum of 2
additional approved AEDs will be allowed. (See Exclusion Criterion No. 10 for
intermittent benzodiazepine rescue parameters.)

2. Subjects receiving felbamate as a concomitant AED must meet the following
criteria: i. Have a 2-year history of felbamate use and a history of a fixed
dosing regimen for a minimum of 60 days prior to Visit 1 (Screening/Baseline).
ii. No prior or known history of hepatotoxicity or hematologic disorder due to
felbamate.

9. Subject with an implanted vagal nerve or deep brain stimulator will be allowed if the
stimulator was implanted at least 5 months prior to Visit 1 (Screening/Baseline) and
the stimulator parameters are not changed for 30 days prior to Visit 1 and for the
duration of the study.

10. Subject taking a ketogenic diet will be allowed as long as the diet has been stable
for at least 3 months prior to Visit 1 (Screening/Baseline) and will remain stable for
the duration of the study.



1. Female subjects who are pregnant (or planning to become pregnant during the study),
lactating, or breast-feeding.

2. Subject has a history o f status epilepticus that required hospitalization within 12
months prior to Visit 1 (Screening/Baseline).

3. Subject has PGTC seizure clusters where individual seizures cannot be counted or
classified.

4. Subject has a history of non-epileptic psychogenic seizures.

5. Subject has a concomitant diagnosis of Partial Onset Seizures (POS).

6. Subject has a clinical diagnosis of Lennox-Gastaut syndrome.

7. Subject is currently taking (within the 30 days prior to Visit 1 [Screening/Baseline])
any of the following medications: diazepam (for any reason other than as intermittent
benzodiazepine rescue medication), phenytoin, mephenytoin, fosphenytoin,
phenobarbital, primidone, ethotoin, clopidogrel, fluvoxamine, amitriptyline,
clomipramine, bupropion, methadone, ifosfamide, cyclophosphamide, or efavirenz.

8. Subject has participated in previous cenobamate clinical studies.

9. Subject has a history of vigabatrin use within 5months prior to Visit 1
(Screening/Baseline), or the subject plans to begin treatment with vigabatrin during
the study.

a) A subject with a history of vigabatrin use that ended more than 5 months prior to
Visit1 may be enrolled after documented evidence of no vigabatrin-associated
clinically significant abnormality in an automated visual perimetry test.

10. Subject has 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) 4 or more times within the
30 days prior to Visit 1 (Screening/Baseline).

11. Subject has received an investigational drug or device within 30 days prior to Visit 1
(Screening/Baseline).

12. Subject has a history of drug or alcohol dependency or abuse within 2 years prior to
Visit 1 (Screening/Baseline).

13. Subject tests positive, via urine drug screen at Visit 1 (Screening/Baseline), for
illicit drugs not legalized in your region/state, or for a drug that has not been
prescribed (e.g., certain opiates).

14. Subject has a history of 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.

15. History of AED-associated rash that involved conjunctiva or mucosae.

16. History of more than one non-serious drug-related hypersensitivity reaction that
required discontinuation of the medication.

17. Subject has evidence of clinically significant abnormalities or disease (e.g.,
psychiatric, cardiac, respiratory, gastrointestinal, hepatic [aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) more than 2 times the upper
limit of normal (ULN), or total or direct bilirubin not more than ULN], or renal
disease) that, in the opinion of the Principal Investigator, could affect the
subject's safety or conduct of the study.

18. Presence of congenital short QT syndrome or relevant replicated change in QT/QTc
interval less than 340 msec on ECG.

19. Subject has any significant active Central Nervous System (CNS) infection,
demyelinating disease, degenerative neurologic disease or any CNS disease deemed to be
progressive during the course of the study that may confound the interpretation of the
study results.

20. Subject has a creatinine clearance less than 50 mL/min, as calculated by
Cockcroft-Gault equation.

21. Subject has an absolute neutrophil count less than 1500/µL.

22. Subject has platelet count lower than 80,000/µL in subjects treated with valproate.

23. Subject has a history of positive antibody/antigen test for hepatitis A, hepatitis B,
hepatitis C, or HIV.

24. Subject has any suicidal ideation (with intent with or without a plan) at Visit 1
(Screening/Baseline) or Visit 4 (Randomization) (i.e., answering YES to Question 4
and/or Question 5 on the Suicidal Ideation section of the C-SSRS).

25. Subject has more than 1 lifetime suicide attempt.

26. Subject is a staff member or immediate family member of study staff.

27. Previous exposure to cenobamate or sensitivity/allergy to components of the oral
suspension.

Any potential exception to the inclusion as well as exclusion criteria allowing de minimis
(clinically trivial and meaningless) variations must be approved by the Medical Monitor.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/07/2024
Actual
Sample size
Target
170
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Austin Health - Heidelberg
Recruitment hospital [2] 0 0
Children's Health Queensland Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
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Arizona
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California
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Illinois
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Kentucky
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Washington
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Bulgaria
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Veliko Tarnovo
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Bulgaria
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Blagoevgrad
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Ruse
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Sofia
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Varna
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Praha
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Ostrava-Vitkovice
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Rychnov Nad Knežnou
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Trencin
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Banská Bystrica
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Krompachy
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Madrid
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Malaga
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Spain
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Valencia
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Ukraine
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Dnipropetrovsk
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Dnipro
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Ivano-Frankivsk
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Kharkiv
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Lviv
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Poltava
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Ternopil
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Ukraine
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Vinnytsya

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
SK Life Science, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This trial is intended to study the safety and effectiveness of an new anti-epileptic drug
(AED) on Primary Generalized Tonic-Clonic (PGTC) Seizures. Eligible Subjects, adults and
adolescents, will continue to take their usual AEDs and receive either cenobamate or placebo.
Subjects will have a 50% chance or receiving cenobamate or placebo (sugar pill). Subjects
will initially receive 12.5 mg of cenobamate or placebo (study drug) and increase the dose
every two weeks until they reach a target dose of 200 mg. Subjects will take study drug at
approximately the same time in the morning (once a day) with or without food. If tolerability
issues arise, dosing can be changed to evening. Also, once a subject reaches 200 mg, the dose
can be decreased one time to 150 mg, if necessary. The treatment period is 22 weeks and there
is a 3 week follow up period, which includes a one week decrease in study drug to 100 mg
prior to stopping. Adolescents will follow the same every two week regimen and receive
cenobamate as an oral suspension based on weight. Subjects who complete may be eligible for
an extension study and will not have to complete the follow up period. Subjects will track
their seizure types and frequency in a diary throughout the study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03678753
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sunita Misra, MD
Address 0 0
SK Life Science, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sunita Misra, MD
Address 0 0
Country 0 0
Phone 0 0
1-402-835-5977
Fax 0 0
Email 0 0
smisra@sklsi.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03678753