Primary Generalized Tonic-Clonic Seizures
Conditions
Keywords
Epilepsy
Brief summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in primary generalized tonic-clonic seizures (PGTCS).
Detailed description
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in subjects diagnosed with generalized epilepsy and experiencing probable or possible PGTCS (with or without other subtypes of generalized seizures), and taking 1 to 3 anti-seizure medications (ASMs). Eligible subjects will be randomly assigned 1:1 to XEN1101 or placebo: subjects aged ≥ 18 years will receive XEN1101 25 mg or placebo, and subjects aged ≥12 years and \<18 years will receive either XEN1101 15 mg, 25 mg, or placebo. Randomization will be stratified based on region, age group, and background use of CYP3A4-inducer ASMs. Eligible subjects will have up to 9.5 weeks durations to assess the baseline frequency of seizures, followed by a double-blind treatment period (DBP) where subjects will receive 12 weeks of blinded treatment. During the DBP, subjects will be instructed to orally take XEN1101 or placebo once daily with an evening meal. Subjects who complete the 12-week DBP will have the opportunity to enroll in a separate open-label-extension (OLE) study for continued treatment with XEN1101. Subjects who do not enroll in the OLE will enter an 8-week post-treatment follow-up period.
Interventions
DRUGXEN1101
XEN1101 capsules
DRUGPlacebo
Placebo capsules
Sponsors
Xenon Pharmaceuticals Inc.
Worldwide Clinical Trials
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median percent change (MPC) in monthly (28 days) PGTCS frequency | Baseline through DBP (Week 12) | Median percent change (MPC) in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects | Baseline through DBP (Week 12) | Proportion of subjects experiencing ≥50% reduction in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo. |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Chile, Croatia, Czechia, France, Germany, Israel, Italy, Mexico, Netherlands, Poland, Portugal, Spain, United Kingdom, United States
Contacts
CONTACTXenon Medical Affairs
STUDY_DIRECTORMedical Director
Xenon Pharmaceuticals Inc.
Outcome results
None listed