Phase 3 study for people with Epilepsy

Reproduced exactly, unedited. Written for researchers rather than for patients.

Key Inclusion Criteria:

1. Subject is properly informed of the nature and risks of the study and gives informed consent in writing prior to entering the study (for adult subjects) and for adolescent subjects parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
2. Subject is ≥12 years of age with a BMI ≤40 kg/m2 at Visit 1.
3. Subject must have had adequate trials of at least 2 ASMs, which were given (and tolerated) at adequate therapeutic doses, without achieving sustained seizure freedom.
4. Subject has probable or possible PGTCS (with or without other subtypes of generalized seizures) for ≥1 year, in the setting of generalized epilepsy according to the International League Against Epilepsy 2017 classification criteria, and subject is approved by The Epilepsy Study Consortium (TESC).
5. Subject is on a stable dose of 1 to 3 allowable current ASMs for at least 3 months prior to the planned randomization (Visit 2), during screening/baseline, and throughout the DBP.
6. Subject is able to keep accurate seizure diaries.

Key Exclusion Criteria:

1. Subject has had status epilepticus within the 12 months prior to Visit 1.

2. Subject has history of repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.

3. Subject has a history of non-epileptic psychogenic seizures within 10 years prior to Visit 1.

4. Subject has a concomitant diagnosis of focal-onset seizures (FOS).

5. Subject has presence or history of a developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.

6. Subject has seizures secondary to drug or alcohol use, ongoing infection, neoplasia, demyelinating disease, degenerative neurological disease, metabolic illness, progressive structural lesion, encephalopathy, or progressive central nervous system (CNS) disease.

7. Subject has history of neurosurgery for seizures <1 year prior to Visit 1, or radiosurgery <2 years prior to Visit 1.

8. Subject has schizophrenia and other psychotic disorders (eg, schizophreniform disorder, schizoaffective disorder, psychosis not otherwise specified), bipolar disorder, or another serious mental health disorder. Subject has uncontrolled unipolar major depression where changes in pharmacotherapy are needed or anticipated during the study.

9. Subject has any clinically significant laboratory abnormalities or clinically significant abnormalities on prestudy physical examination, vital signs, or ECG that, in the judgment of the investigator, indicate a medical problem that would preclude study participation, including but not limited to:

   a. History or presence of long QT syndrome; QTcF >450 msec at baseline; family history of sudden death of unknown cause.

10. Any personal circumstance that, in the opinion of the investigator, prevents adherence to the protocol.

The criteria to be eligible for randomization are:

1. During the last 56 days that preceded the randomization visit (Visit 2), subject must have had a sufficient documented seizure frequency of PGTCS, including ≥1 PGTCS during each of the first and second 4-week periods preceding randomization. Retrospective seizure data documented up to 4 weeks prior to Visit 1 may be used in combination with a minimum of 4 weeks of prospective seizure data recorded in the study eDiary.
2. Study eDiary was completed a minimum of 80% of all applicable days during the last 28-56 days of the baseline period that preceded randomization as evidence of adequate compliance (eg, >45 of 56 days, if no retrospective data prior to Visit 1 are used).
3. Subject did not change dose of, stop, or initiate any new ASM(s) during the 3 months that preceded randomization and plans on maintaining a stable dose of ASM(s) during the DBP.