X-TOLE2: A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures
Study Details
Study Description
Brief Summary
The X-TOLE2 Phase 3 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive therapy in focal-onset seizures.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Approximately 360 subjects will be randomized in a blinded manner to one of two active treatment groups or placebo in a 1:1:1 fashion (XEN1101 25 mg : 15 mg : Placebo). Eligible subjects will have up to 9.5 weeks of baseline to assess frequency of seizures, followed by 12 weeks of blinded treatment. In order to be included in the study, subjects must be treated with a stable dose of 1 to 3 allowable antiseizure medications (ASMs) for at least one month prior to screening, during baseline, and throughout the double-blind treatment period (DBP) of the study. 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 qualify and enroll in a separate open-label extension (OLE) study for continued treatment with XEN1101. Subjects who do not enroll in the OLE will enter a 6-week post treatment follow-up period.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: XEN1101 25 mg/day XEN1101 25 mg/day |
Drug: XEN1101
XEN1101 capsules
|
| Experimental: XEN1101 15 mg/day XEN1101 15 mg/day |
Drug: XEN1101
XEN1101 capsules
|
| Placebo Comparator: Placebo Placebo |
Drug: Placebo
Placebo capsules
|
Outcome Measures
Primary Outcome Measures
- To assess the effect of XEN1101 versus placebo on reducing focal seizure frequency. [From baseline (9.5 weeks prior to Day 0) through to the final dose (up to Day 84)]
Median percent change (MPC) in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo.
Secondary Outcome Measures
- Proportion of subjects experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline through the DBP for XEN1101 versus placebo. [From baseline (9.5 weeks prior to Day 0) through to the final dose (up to Day 84).]
- To assess the early treatment effect of XEN1101 versus placebo on focal seizure frequency. [From baseline (9.5 weeks prior to Day 0) through to the final dose (up to Day 84).]
MPC in weekly (7 days) focal seizure frequency from baseline to Week 1 for XEN1101 versus placebo.
- To assess the effect of XEN1101 versus placebo on seizure impact. [From baseline (9.5 weeks prior to Day 0) through to Week 12 visit.]
Proportion of subjects experiencing "at least much improved" (including "much" and "very much improved") in Patient Global Impression of Change (PGI-C).
- To assess the safety and tolerability of XEN1101 (e.g., adverse events). [From screening (up to 9.5 weeks prior to baseline) through to 42 days post-final dose.]
To assess adverse events as criteria for safety and tolerability.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
-
Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017)
-
Treatment with a stable dose of 1 to 3 allowable current ASMs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
-
Able to keep accurate seizure diaries
Exclusion Criteria:
-
Previously documented electroencephalogram which shows any pattern not consistent with focal etiology of seizures.
-
History of focal aware non-motor seizures, non-epileptic psychogenic seizure, primary generalized seizure, developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
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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.
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History of status epilepticus or repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
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History of neurosurgery for seizures <1 year prior to Visit 1, or radiosurgery <2 years prior to enrollment.
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Any medical condition or personal circumstance that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hawaii Pacific Neuroscience | Honolulu | Hawaii | United States | 96817 |
| 2 | Northeast Epilepsy Group | Hackensack | New Jersey | United States | 07601 |
Sponsors and Collaborators
- Xenon Pharmaceuticals Inc.
- Worldwide Clinical Trials
Investigators
- Study Director: Medical Director, Xenon Pharmaceuticals Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XPF-010-301