Focal Onset Epilepsy, Focal Onset Seizure
Conditions
Keywords
Epilepsy, focal seizure, sodium channel, voltage-gated, alpha subunit, Nav1.6 inhibitor, Antiseizure medication, ASM, Antiepileptic drug, AED, partial seizure, partial onset epilepsy
Brief summary
This study will evaluate the safety, pharmacokinetics, and efficacy of three different doses of NBI-921352 versus placebo in adults with focal onset seizures
Interventions
DRUGNBI-921352
Tablets for oral administration
DRUGPlacebo
Matching placebo tablets for oral administration
Sponsors
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Capable of providing consent and has completed the written informed consent. 2. Male or female, 18 to 65 years of age, inclusive, with a body mass index (BMI) \< 40 kg/m\^2. 3. Diagnosis of focal onset epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017) at least 18 months before screening. 4. History of uncontrolled seizures despite adequate treatment with at least 1 anti-seizure medication (ASM) for at least 18 months prior to screening. 5. Treatment with at least 1 but not more than 4 ASMs for at least 1 month before screening, during the baseline seizure diary data collection, and throughout the duration of the study. 6. Be able to keep accurate seizure diaries. 7. Documented seizure frequency in the baseline seizure diary of ≥8 countable focal seizures during the 8-week seizure baseline period. Key
Exclusion criteria
1. History of epilepsy with only nonmotor seizures without an observable component, psychogenic nonepileptic seizures, or primary generalized seizures. 2. Presence or previous history of developmental and/or epileptic encephalopathy. 3. Presence of seizure types other than FOS. 4. Status epilepticus within the last 12 months before enrollment. 5. Any suicidal behavior or suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent) based on the C-SSRS in the 2 years before screening, a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt. 6. Multiple drug allergies or a severe drug reaction to an ASM(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions. 7. An implanted responsive neurostimulator system (RNS).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Serious Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation of Study Treatment, and Fatal TEAEs | Through Week 15 |
| NBI-921352 exposure-efficacy response relationship, defined as the slope of the relationship between reduction in monthly focal onset seizure frequency and plasma concentration at steady state | Baseline to Week 11 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants with a ≥ 50% reduction in monthly (28 days) focal onset seizure frequency during the treatment period | Baseline and Weeks 1 to 11 |
| Percent Change from Baseline in Monthly Focal Onset Seizure Frequency During the Treatment Period | Baseline and Weeks 1 to 11 |
| Percent Change from Baseline in Monthly Focal Onset Seizure Frequency During the Maintenance period | Baseline and Weeks 4 to 11 |
| Clinical Global Impression of Change (CGIC) Scores at Week 11 | Week 11 |
Countries
Australia, Belgium, Czechia, France, Hungary, Italy, Spain
Outcome results
None listed