Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
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| ClinicalTrials.gov Identifier: NCT05219617 |
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Recruitment Status :
Recruiting
First Posted : February 2, 2022
Last Update Posted : May 6, 2024
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Sponsor:
SK Life Science, Inc.
Information provided by (Responsible Party):
SK Life Science, Inc.
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Brief Summary:
The primary objective is to evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the number of drop seizures (tonic, atonic, and tonic-clonic) compared with placebo in pediatric and adult subjects (age 4-55 years) diagnosed with Lennox Gastaut Syndrome (LGS).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Seizures Lennox Gastaut Syndrome | Drug: Carisbamate | Phase 3 |
The secondary objectives are:
- To evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the total number of seizures compared with placebo in pediatric and adult subjects diagnosed with Lennox Gastaut Syndrome (LGS)
- Evaluate the safety, tolerability of carisbamate in the LGS population
- Evaluate steady-state pharmacokinetics of carisbamate in subjects with Lennox Gastaut.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 252 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | This double-blind, randomized, placebo-controlled study will evaluate the efficacy of carisbamate 200 mg BID or the pediatric equivalent dose and 300 mg BID or the pediatric equivalent dose for the treatment of seizures associated with Lennox Gastaut syndrome in subjects 4 to 55 years of age. |
| Masking: | Double (Participant, Care Provider) |
| Masking Description: | Double-blind study |
| Primary Purpose: | Treatment |
| Official 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 |
| Actual Study Start Date : | April 28, 2022 |
| Estimated Primary Completion Date : | June 2025 |
| Estimated Study Completion Date : | June 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lennox-Gastaut syndrome
MedlinePlus related topics:
Seizures
| Arm | Intervention/treatment |
|---|---|
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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 |
Drug: 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]). |
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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 |
Drug: 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]). |
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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 |
Drug: 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]). |
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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 |
Drug: 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]). |
Primary Outcome Measures :
- 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. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509
Secondary Outcome Measures :
- 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. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509
- Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509
- Subject/Caregiver Global Impression of Change (S/CGIC) in overall condition score at the last visit. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509- Scoring will be from 1 to 7 with 1 (very much improved) to 7 (very much worse)
Other Outcome Measures:
- Percentage change from baseline in the 28-day frequency of: drop seizures (tonic, atonic, tonic-clonic); non-drop seizures (myoclonic seizures, atypical absence); total seizures during the maintenance phase of the double-blind treatment period. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509
- Percentage change from baseline in non-drop seizures (myoclonic seizures, atypical absence) frequency per 28 days during the during the double-blind treatment period. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509
- 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 maintenance phase of the double-blind treatment period. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509
- Proportion of subjects with a 75%, 90% and 100% response rate for drop seizures (tonic, atonic, tonic-clonic), non-drop seizures, and total seizures during the double-blind treatment period. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509
- Proportion of subjects with a 75%, 90% and 100% response rate for drop seizures (tonic, atonic, tonic-clonic), non-drop seizures, and total seizures during the maintenance phase of the double-blind treatment period. [ Time Frame: 3 years ]Efficacy of Carisbamate YKP509
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| Ages Eligible for Study: | 4 Years to 55 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Subject must have a documented history of Lennox-Gastaut syndrome by:
- Evidence of more than one type of seizure, of which at least one should be an atonic or tonic seizure
- History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow, spike and wave pattern <3.0 Hz)
- History of developmental delay
- Male or female subjects
- Subjects must be age 4-55 years at the time of consent/assent
- Must have been <11 years old at the onset of LGS
- 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).
- 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
- 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.
- 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.
- Parents or caregivers must be able to keep accurate seizure diaries
- 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.
- Subject and/or caregiver(s)/legal representative must be willing and able to give informed assent/consent for participation in the study
- Subject and their caregiver must be willing and able (in the investigator's opinion) to comply with all study requirements
- History of COVID-19 vaccination is permitted
Exclusion Criteria:
- 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
- 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
- Subjects who were on adrenocorticotropic hormone (ACTH) therapy in the 6 months prior to baseline
- Subject on dietary therapy for less than 4 weeks prior to screening visit (Visit 1) or suffers from frequent stooling
- Current use of felbamate with less than 18 months of continuous exposure
- 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.
- Subject who had a history of hypoxia which needed emergency resuscitation within 12 months prior to baseline
- Status epilepticus within 12 weeks prior to Visit 1
- Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit 1, as evaluated by the Investigator
- Subject has clinically significant abnormal laboratory values, in the investigator's opinion, at Visit 1 or time of randomization (Visit 2)
- 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
- 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.
- Subject is pregnant, may be pregnant, lactating or planning to be pregnant
- 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
- 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.
- 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
- Subject with total bilirubin [TBL] >2 x ULN (except for Gilbert's syndrome).
- Active viral hepatitis (B or C) as demonstrated by positive serology at the Screening visit (Visit 1)
- History of positive antibody/antigen test for human immunodeficiency virus (HIV)
- If taking Epidiolex, subject may not use other approved cannabidiol or over the counter cannabidiol products
- Scheduled for epilepsy-related surgery, VNS insertion, or any other stimulators/surgery during the projected course of the study
- Subject who has taken or used any investigational drug or device in the 4 weeks prior to the screening visit (Visit 1)
- 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
- Evidence of cardiac disease, including unstable angina, myocardial infarction, within the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT syndrome
- Subject with a short QTc interval (<340 msec) or long QTc interval (>460 msec) as confirmed by a repeated electrocardiogram (ECG)
- Benzodiazepine rescue administered on average more than once a week in the month before Visit 1
- Previous exposure to carisbamate or sensitivity/allergy to components of the oral suspension.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05219617
Contacts
| Contact: Barbara Remes | 201-421-3810 | bremes@sklsi.com |
Locations
Show 69 study locations
Sponsors and Collaborators
SK Life Science, Inc.
Investigators
| Study Director: | Marc Kamin, MD | SK Life Science, Inc. |
| Responsible Party: | SK Life Science, Inc. |
| ClinicalTrials.gov Identifier: | NCT05219617 |
| Other Study ID Numbers: |
YKP509C003 |
| First Posted: | February 2, 2022 Key Record Dates |
| Last Update Posted: | May 6, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by SK Life Science, Inc.:
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Seizures Lennox Gastaut Syndrome Pediatrics Adults |
Additional relevant MeSH terms:
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Seizures Lennox Gastaut Syndrome Syndrome Disease Pathologic Processes Neurologic Manifestations |
Nervous System Diseases Epileptic Syndromes Epilepsy Brain Diseases Central Nervous System Diseases Genetic Diseases, Inborn |