Cenobamate (YKP3089) is a small molecule approved in the United States (US), Europe and several other countries around the world for the treatment of Partial-Onset (focal) seizures in adult subjects (≥18 years of age). In the US it is approved for use as monotherapy, however, there is little clinical data assessing its use as monotherapy in adults with POS. This study is designed to explore the effectiveness of doses of 100 mg/day and 200 mg/day as monotherapy in adult subjects with newly diagnosed or recurrent POS/focal onset epilepsy.
This is an uncontrolled, single-arm, open-label, Phase IV study conducted at approximately 40 sites in the US. It will consist of the following Periods: 1. Pretreatment Period (up to 21 days) 2. 100 mg/day Treatment Period (6-week Titration Phase, 26-week Maintenance Phase) 3. 200 mg/day Treatment Period (2-week Titration Phase, 26-week Maintenance Phase) 4. 26-week Optional Extension Period 5. Follow Up Period (4 weeks) Pretreatment Period At the screening visit (Visit 1) the investigator will obtain informed consent and assess the subject for their eligibility to participate in the study. The investigator will review any available hematology, chemistry blood tests, and ECGs. Vital signs and routine physical and neurological exam will be performed. 100 mg/day Treatment Period Subjects who complete screening and meet the inclusion/exclusion criteria begin the 32-week Treatment Period which includes a 6-week Titration Phase and a 26-week Maintenance Phase. During the Titration Phase subjects will be treated with cenobamate 12.5 mg/day for two weeks, 25 mg/day for two weeks and 50 mg/day for two weeks. Subjects tolerating cenobamate at the end of the Titration Phase will continue treatment with 100 mg/day in the Maintenance Phase for 26 weeks. At the end of the Maintenance Phase, the subject will have the option of continuing on in a 26-week Extension Period or discontinuing cenobamate. Subjects who experience a certain type of seizure during the 100 mg/day Maintenance Phase (with or without rescue medication use) will transition to the 200 mg/day Treatment Period. 200 mg/day Treatment Period: The 200 mg/day Treatment Period consists of a 2-week Titration Phase and a 26-week Maintenance Phase. During the 2-week Titration Phase, subjects will receive cenobamate 150 mg/day before entering the 26-week 200 mg/day Maintenance Phase. At the end of the Maintenance Phase, the subject will have the option of continuing on in a 26-week Extension Period or discontinuing cenobamate. If the subject experiences a certain type of seizure at 200 mg/day during the Maintenance Phase, then they will be discontinued from the study. Optional Extension Period: An Optional Extension Period will last 26 weeks. During the Optional Extension Period, Visits will occur at 13th week (Day 315/287a, Visit 8/8a) and 26th week (Day 406/378a, Visit 9/9a) to record vital signs and identify adverse events and occurrence of a seizure using a seizure diary. If a certain type of seizure occurs during the Optional Extension Period, the subject will be discontinued from the study. Follow-up Period: If a subject prematurely discontinues from the study, is not continuing into the Optional Extension Period or completes the last visit in the Optional Extension Period, cenobamate should either be discontinued or will be titrated down by 50% for two weeks and then discontinued depending on the current dose. A follow-up visit should occur two weeks after the date of cenobamate discontinuation except in specific circumstances.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
The 100 mg/ day Treatment Period includes a 6-week Titration Phase and a 26-week Maintenance Phase. During the Titration Phase subjects will be treated with cenobamate 12.5 mg/day for two weeks, 25 mg/day for two weeks and 50 mg/day for two weeks. Subjects tolerating cenobamate at the end of the Titration Phase will continue treatment with 100 mg/day in the Maintenance Phase for 26 weeks. If the subject does not experience a certain type of seizure in the 100 mg/day Maintenance Phase, he/she can enter the Optional Extension Period (100 mg/day). The 200 mg/day treatment period consists of a 2-week Titration Phase and a 26-week Maintenance Phase. During the 2-week Titration Phase, subjects will receive cenobamate 150 mg/day before entering the 26-week 200 mg/day Maintenance Phase. If the subject does not experience a certain type of seizure during the 200 mg/day Maintenance Phase, he/she can enter the 26 week Optional Extension Period (200 mg/day).
Arizona Neuroscience Research
Phoenix, Arizona, United States
Center For Neurosciences
Tucson, Arizona, United States
Clinical Trials Inc
Little Rock, Arkansas, United States
Neuro Pain Medical Center
Fresno, California, United States
Hoag Physician Partners
Newport Beach, California, United States
Hartford Hospital
Hartford, Connecticut, United States
Yale School of Medicine - Yale-New Haven Hospital
New Haven, Connecticut, United States
Elite Clinical Research
Miami, Florida, United States
Knight Neurology
Rockledge, Florida, United States
Consultants In Epilepsy and Neurology
Boise, Idaho, United States
...and 9 more locations
Seizure-freedom during the 26-week Maintenance Phase of the 100 mg/day Treatment Period
The number (percentage) of subjects with POS who achieved seizure-freedom during the 26-week Maintenance Phase of the 100 mg/day Treatment Period.
Time frame: 32 weeks
Seizure freedom during each of the 26-week Maintenance Phases
The number (percentage) of subjects with POS who achieved seizure freedom during each of the 26-week Maintenance Phases regardless of cenobamate dose (last evaluated dose of 100 mg/day or 200 mg/day).
Time frame: 60 weeks
Time to first seizure onset
Time to first seizure onset (defined as the period from the first cenobamate dose in the Maintenance Phase to first seizure onset).
Time frame: 52 weeks
Time to withdrawal from the study
Time to withdrawal from the study (defined as the period from the first dose of cenobamate in the Maintenance Phase to the date of study withdrawal).
Time frame: 86 weeks
Number (percentage) of subjects with POS who achieved seizure freedom during the 52-week treatment
The number (percentage) of subjects with POS who achieved seizure freedom during the 52-week treatment (ie, 26-week Maintenance Phase plus Optional 26-week Extension Period).
Time frame: 52 weeks
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