CARISBAMATE for Lennox-Gastaut syndrome

Inclusion criteria

• {"criterion_text":"- 1. Subject must have a documented history of Lennox-Gastaut syndrome by: a. Evidence of more than one type of seizure, of which at least one should be an atonic or tonic seizure\n- 1. Subject must have a documented history of Lennox-Gastaut syndrome by: b. History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow, spike and wave pattern <3.0 Hz)\n- 1. Subject must have a documented history of Lennox-Gastaut syndrome by: c. History of developmental delay\n- 2. Male or female subjects\n- 3. Subjects must be age 4-55 years at the time of consent/assent\n- 4. Must have been <11 years old at the onset of LGS\n- 5. Subjects must have experienced at least 8 drop seizures with potential to fall (tonic, atonic, tonic-clonic) during the 4-week Baseline period preceding randomization (minumim of 4 drop seizures in the first two weeks and 4 in the last two weeks). Drop seizures are defined as a countable 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).\n- 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\n- 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.\n- 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.\n- 9. Parents or caregivers must be able to keep accurate seizure diaries\n- 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 2 weeks after dose of study drug.\n- 11. Subject and/or caregiver/legal representative must be willing and able to give informed assent/consent for participation in the study\n- 12. Subject and their caregiver must be willing and able (in the investigator's opinion) to comply with all study requirements\n- 13. History of COVID-19 vaccination is permitted."}

Exclusion criteria

• {"criterion_text":"- 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\n- 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\n- 3. Subjects who were on adrenocorticotropic hormone (ACTH) therapy in the 6 months prior to baseline\n- 4. Subject on dietary therapy for less than 4 weeks prior to screening visit (Visit 1) or suffers from frequent stooling\n- 5. Current use of felbamate with less than 12 months of continuous exposure\n- 6. Subjects who took vigabatrin in the past must have discontinued it at least 5 months before Visit 1. Subjects taking vigabatrin should have documentation showing no evidence of a vigabatrin-associated visual field abnormality.\n- 7. Subject who had a history of hypoxia which needed emergency resuscitation within 12 months prior to baseline\n- 8. Status epilepticus within 12 weeks prior to Visit 1\n- 9. Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit 1, as evaluated by the Investigator\n- 10. Subject has clinically significant abnormal laboratory values, in the investigator's opinion, at Visit 1 or time of randomization (Visit 2)\n- 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\n- 12. Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), Responsive Neurostimulator System (RNS) or other neurostimulation for epilepsy device implanted or activated <5 months 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.\n- 13. Subject is pregnant, may be pregnant, lactating or planning to be pregnant\n- 14. Any suicidal ideation with intent, with or without a plan within 6 months before Visit 2 (i.e., answering \"Yes\" to question 4 or 5 in the Suicidal Ideation section of the age specific Columbia-Suicide Severuty Rating Scale (C-SSRS) in subjects aged 6 years and above who are able to be evaluated.\n- 15. Any suicidal behavior within 2 years before Visit 2 (i.e., answering YES to any questions in the Suicidal behavior section of the age-specifc Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and above who are able to be evaluated.\n- 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\n- 17. Subject with total bilirubin [TBL] >2 x ULN (except for Gilbert's syndrome).\n- 18. Active viral hepatitis (B or C) as demonstrated by positive serology at the Screening visit (Visit 1)\n- 19. History of positive antibody/antigen test for human immunodeficiency virus (HIV)\n- 20. If taking Epidiolex, subject may not use other approved cannabidiol or over the counter cannabidiol products\n- 21. Scheduled for epilepsy-related surgery, VNS insertion, or any other stimulators/surgery during the projected course of the study\n- 22. Subject who has participated in any clinical study of an investigational product or device in the 30 days prior to the screening visit (Visit 1)\n- 23. Concomitant use of medications known to be strong inducers of cytochrome UGT enzymes 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\n- 24. Evidence of cardiac disease, including unstable angina, myocardial infarction, within the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT syndrome\n- 25. Subject with a short QTcF interval (<340 msec) or long QTcF interval (>460 msec) as confirmed by a repeated electrocardiogram (ECG)\n- 26. Intermittent benzodiazepine rescue administered more than four times in the 28 days prior to Visit 1 (1 to 2 doses in a 24-hour period is considered as one rescue).\n- 27. Previous exposure to carisbamate or sensitivity/allergy to components of the oral suspension."}

Primary endpoints

• {"endpoint_text":"- The 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) during the double-blind treatment period.","definition_or_measurement_approach":"Percentage change from baseline in the total frequency (average per 28 days) of countable drop seizures with potential to fall (tonic, atonic, tonic‑clonic) measured during the double-blind treatment period."}

Secondary endpoints

• {"endpoint_text":"- 1. The percentage of subjects with at least a 50% reduction from baseline in the total frequency of countable drop seizures (tonic, atonic, tonic-clonic) during the double-blind treatment period.","definition_or_measurement_approach":"Proportion of subjects achieving ≥50% reduction from baseline in total frequency of countable drop seizures during the double-blind treatment period."}
• {"endpoint_text":"- 2. Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period.","definition_or_measurement_approach":"Percentage change from baseline in total seizure frequency (all seizure types) during the double‑blind treatment period."}
• {"endpoint_text":"- 3. Subject/Caregiver Global Impression of Change in overall condition (S/CGI-C) score at the last visit.","definition_or_measurement_approach":"S/CGI-C score assessed at the last visit to capture global impression of change by subject/caregiver."}
• {"endpoint_text":"- 4. Please refer to the Protocol for further Secondary endpoints.","definition_or_measurement_approach":"Refer to protocol for definitions and measurement approaches for additional secondary endpoints."}

Germany

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

26-06-2024

Processing Time Days

19

Number Of Sites

2

Number Of Participants

12

Greece

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

22-07-2024

Processing Time Days

45

Number Of Sites

1

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

26-06-2024

Processing Time Days

19

Number Of Sites

6

Number Of Participants

8

Portugal

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

24-06-2024

Processing Time Days

17

Number Of Sites

2

Number Of Participants

23

Spain

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

21-06-2024

Processing Time Days

14

Number Of Sites

2

Number Of Participants

9

Poland

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

24-06-2024

Processing Time Days

17

Number Of Sites

2

Number Of Participants

24

Hungary

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

20-06-2024

Processing Time Days

13

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Sk Life Science Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Iqvia Rds Inc.

Responsibilities

code 8

Name

PPD Global Ltd.

Responsibilities

Project management duties and monitoring/regulatory

Name

PPD Development LP

Responsibilities

codes 1,12,2,6

Name

Suvoda LLC

Responsibilities

code 3

Name

Medidata Solutions Inc.

Responsibilities

code 6

Name

PCI Pharma Services Germany GmbH

Responsibilities

This site is responsible for certification of (list thenumber(s) of each IMP including placebo

Name

PPD Global Central Labs

Responsibilities

code 4

Third parties

• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"Project management duties and monitoring/regulatory","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"code 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"This site is responsible for certification of (list thenumber(s) of each IMP including placebo","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"codes 1,12,2,6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 6","organisation_type":"Non-Pharmaceutical company"}