Open-label Study of Cenobamate Monotherapy in Adult Subjects With Newly Diagnosed or Recurrent Partial-Onset Epilepsy
brief summary
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.
detailed description
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.