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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05219617




Registration number
NCT05219617
Ethics application status
Date submitted
6/01/2022
Date registered
2/02/2022

Titles & IDs
Public title
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Carisbamate (YKP509) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults, With Optional Open-Label Extension
Secondary ID [1] 0 0
YKP509C003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Seizures 0 0
Lennox Gastaut Syndrome 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

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

Experimental: Carisbamate 200 mg BID arm - Age: 4 to \<12y\* Titration: 2 mg/kg BID Maintenance: 4 mg/kg BID

Age: =12 y Titration: 100 mg BID Maintenance: 200 mg BID

Experimental: Carisbamate 300 mg BID arm - Age: 4 to \<12y\* Titration: 2.75 mg/kg BID Maintenance: 5.5 mg/kg BID

Age: =12 y Titration: 150 mg BID Maintenance: 300 mg BID

Placebo comparator: Placebo matched to 200 mg BID arm - Age: 4 to \<12y\* Titration: Volume equivalent to 2 mg/kg BID Maintenance: Volume equivalent to 4 mg/kg BID

Age: =12 y Titration: Volume equivalent to 100 mg BID Maintenance: Volume equivalent to 200 mg BID

Placebo comparator: Placebo matched to 300 mg BID arm - Age: 4 to \<12y\* Titration: Volume equivalent to 2.75 mg/kg BID Maintenance: Volume equivalent to 5.5 mg/kg BID

Age: =12 y Titration: Volume equivalent to 150 mg BID Maintenance: Volume equivalent to 300 mg BID


Treatment: Drugs: Carisbamate
Adolescent subjects 12 to 18 years old will receive the same dose as adults. Subjects 4 to \< 12 years old in the carisbamate 200 mg BID arm will receive 4 mg/kg BID (not to exceed 200 mg BID \[or a total of 400 mg per day\]).

Subjects 4 to \< 12 years old in the carisbamate 300 mg BID arm will receive 5.5 mg/kg BID (not to exceed 300 mg BID \[or a total of 600 mg per day\]).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary outcome will be the percentage change from baseline in the total frequency (average per 28 days) of countable drop seizures with potential to fall (tonic, atonic, tonic-clonic) seizures during the double-blind treatment period.
Timepoint [1] 0 0
3 years
Secondary outcome [1] 0 0
The percentage of subjects with at least a 50% reduction from baseline in the total frequency of drop seizures (tonic, atonic, tonic-clonic) during the double-blind treatment period.
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period.
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Subject/Caregiver Global Impression of Change (S/CGIC) in overall condition score at the last visit.
Timepoint [3] 0 0
3 years

Eligibility
Key inclusion criteria
1. Subject must have a documented history of Lennox-Gastaut syndrome by:

1. Evidence of more than one type of seizure, of which at least one should be an atonic or tonic seizure
2. History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow, spike and wave pattern <3.0 Hz)
3. History of developmental delay
2. Male or female subjects
3. Subjects must be age 4-55 years at the time of consent/assent
4. Must have been <11 years old at the onset of LGS
5. Subjects must have experienced at least 2 drop seizures with potential to fall (tonic, atonic, tonic-clonic) during the 4-week Baseline period preceding randomization (minimum of 4 drop seizures in the first two weeks and 4 in the last two weeks). Drop seizures are defined as a seizure involving the entire body, trunk, or head that led or could have led to a fall, injury, slumping in a chair, or hitting the subject's head on a surface. All drop seizure types must be countable (either as isolated seizures or as countable isolated seizures in a cluster).
6. Subjects must have been receiving 1 to 4 concomitant anti-seizure medications (ASMs) at a stable dose for at least 4 weeks before Visit 1
7. If not taking Epidiolex, subjects may take other approved cannabidiol or over the counter cannabidiol products. If taking cannabidiol other than Epidiolex, consult Medical Monitor to determine if it counts as a concomitant ASM.
8. Dietary therapy and any CNS stimulator settings must be stable for 4 weeks prior to baseline and maintain stable regimen throughout the study. The dietary therapy and CNS stimulators are not counted as an ASM.
9. Parents or caregivers must be able to keep accurate seizure diaries
10. Subject is either not of childbearing potential, defined as premenarchal, postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), if of childbearing potential, must comply with an acceptable method of birth control during the study, for at least 4 weeks prior to study entry and for 4 weeks following completion of the study, if able.
11. Subject and/or caregiver(s)/legal representative must be willing and able to give informed assent/consent for participation in the study
12. Subject and their caregiver must be willing and able (in the investigator's opinion) to comply with all study requirements
13. History of COVID-19 vaccination is permitted
Minimum age
4 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Etiology of subject's seizures is a progressive neurologic disease. Subjects with tuberous sclerosis will not be excluded from study participation, unless there is a progressive brain tumor
2. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease, hepatic disease) that in the opinion of the investigator(s) could affect the subject's safety or study conduct
3. Subjects who were on adrenocorticotropic hormone (ACTH) therapy in the 6 months prior to baseline
4. Subject on dietary therapy for less than 4 weeks prior to screening visit (Visit 1) or suffers from frequent stooling
5. Current use of felbamate with less than 18 months of continuous exposure
6. Concomitant use of vigabatrin: subjects who took vigabatrin in the past must be discontinued for at least 5 months before Visit 1 and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test, if able.
7. Subject who had a history of hypoxia which needed emergency resuscitation within 12 months prior to baseline
8. Status epilepticus within 12 weeks prior to Visit 1
9. Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit 1, as evaluated by the Investigator
10. Subject has clinically significant abnormal laboratory values, in the investigator's opinion, at Visit 1 or time of randomization (Visit 2)
11. Subject has a history of any serious drug-induced hypersensitivity, e.g., toxic epidermal necrolysis, or Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]) or any drug-related rash requiring hospitalization
12. Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), Responsive Neurostimulator System (RNS) or other neurostimulation for epilepsy device implanted or activated <5 months year prior to enrollment. Stimulation parameters that have been stable for <4 weeks, or Battery life of unit not anticipated to extend for duration of trial.
13. Subject is pregnant, may be pregnant, lactating or planning to be pregnant
14. Any suicidal ideation with intent, with or without a plan within 6 months before Visit 2 (i.e., answering "Yes" to questions 4 or 5 in the Suicidal Ideation section of the age- specific Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and above who are able to be evaluated
15. Any suicidal behavior within 2 years before Visit 2 (i.e., answering YES to any question in the Suicidal behavior section of the age-specific Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and above who are able to be evaluated.
16. Evidence of significant active hepatic disease. Stable elevations of liver enzymes (alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) due to concomitant medication(s) will be allowed if they are <3 x ULN
17. Subject with total bilirubin [TBL] >2 x ULN (except for Gilbert's syndrome).
18. Active viral hepatitis (B or C) as demonstrated by positive serology at the Screening visit (Visit 1)
19. History of positive antibody/antigen test for human immunodeficiency virus (HIV)
20. If taking Epidiolex, subject may not use other approved cannabidiol or over the counter cannabidiol products
21. Scheduled for epilepsy-related surgery, VNS insertion, or any other stimulators/surgery during the projected course of the study
22. Subject who has taken or used any investigational drug or device in the 4 weeks prior to the screening visit (Visit 1)
23. Concomitant use of medications known to be strong inducers of cytochrome P450 (CYP3A) including, but not limited to: phenobarbital, phenytoin, carbamazepine, primidone, rifampin, troglitazone, St. John's Wort, efavirenz, nevirapine, glucocorticoids (other than topical usage), modafinil, pioglitazone, and rifabutin
24. Evidence of cardiac disease, including unstable angina, myocardial infarction, within the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT syndrome
25. Subject with a short QTc interval (<340 msec) or long QTc interval (>460 msec) as confirmed by a repeated electrocardiogram (ECG)
26. Benzodiazepine rescue administered on average more than once a week in the month before Visit 1
27. Previous exposure to carisbamate or sensitivity/allergy to components of the oral suspension.

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

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
28/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2026
Actual
Sample size
Target
252
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Austin Hosptial - Heidelberg
Recruitment hospital [2] 0 0
Alfred Health - Melbourne
Recruitment hospital [3] 0 0
Perth's Children Hospital - Nedlands
Recruitment hospital [4] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
- Heidelberg
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment postcode(s) [4] 0 0
- South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Idaho
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Argentina
State/province [15] 0 0
Cordoba
Country [16] 0 0
Argentina
State/province [16] 0 0
Mendoza
Country [17] 0 0
Colombia
State/province [17] 0 0
Barranquilla
Country [18] 0 0
Colombia
State/province [18] 0 0
Cali
Country [19] 0 0
Colombia
State/province [19] 0 0
Envigado
Country [20] 0 0
Colombia
State/province [20] 0 0
Medellín
Country [21] 0 0
Germany
State/province [21] 0 0
Bayern
Country [22] 0 0
Germany
State/province [22] 0 0
Sachsen
Country [23] 0 0
Greece
State/province [23] 0 0
Attiki
Country [24] 0 0
Israel
State/province [24] 0 0
Tel Aviv
Country [25] 0 0
Israel
State/province [25] 0 0
Be'er Sheva
Country [26] 0 0
Israel
State/province [26] 0 0
Jerusalem
Country [27] 0 0
Israel
State/province [27] 0 0
Ramat Gan
Country [28] 0 0
Italy
State/province [28] 0 0
Liguria
Country [29] 0 0
Italy
State/province [29] 0 0
Lombardia
Country [30] 0 0
Italy
State/province [30] 0 0
Calambrone
Country [31] 0 0
Italy
State/province [31] 0 0
Milano
Country [32] 0 0
Italy
State/province [32] 0 0
Verona
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Daegu
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Mexico
State/province [35] 0 0
Jalisco
Country [36] 0 0
Mexico
State/province [36] 0 0
Culiacán
Country [37] 0 0
Mexico
State/province [37] 0 0
Mexico City
Country [38] 0 0
Poland
State/province [38] 0 0
Wielkopolskie
Country [39] 0 0
Poland
State/province [39] 0 0
Kraków
Country [40] 0 0
Portugal
State/province [40] 0 0
Setubal
Country [41] 0 0
Portugal
State/province [41] 0 0
Lisboa
Country [42] 0 0
Portugal
State/province [42] 0 0
Porto
Country [43] 0 0
Serbia
State/province [43] 0 0
Belgrade
Country [44] 0 0
Serbia
State/province [44] 0 0
Kragujevac
Country [45] 0 0
Serbia
State/province [45] 0 0
Niš
Country [46] 0 0
Serbia
State/province [46] 0 0
Novi Sad
Country [47] 0 0
Spain
State/province [47] 0 0
Barcelona
Country [48] 0 0
Spain
State/province [48] 0 0
Madrid
Country [49] 0 0
Taiwan
State/province [49] 0 0
Taipei
Country [50] 0 0
Taiwan
State/province [50] 0 0
Taoyuan

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Marc Kamin, 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
Barbara Remes
Address 0 0
Country 0 0
Phone 0 0
201-421-3810
Fax 0 0
Email 0 0
bremes@sklsi.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05219617