An Open-label Study of XEN1101 in Epilepsy

Study Overview
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Brief Summary
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This study will evaluate the long term safety, tolerability, PK, and efficacy of XEN1101 25 mg QD taken orally in subjects with Focal Onset Seizures (FOS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) for the treatment of seizures for up to 3 years.

Detailed Description
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This is an Open Label Extension study of the following Phase 3 clinical studies: XPF-010-301 (X-TOLE2), XPF-010-302 (X-TOLE3), and XPF-010-303 (X-ACKT). This study will evaluate the long term safety, tolerability, PK, and efficacy of XEN1101 25 mg QD taken orally once daily (QD) in subjects with FOS or PGTCS for the treatment of seizures for up to 3 years. Subjects who successfully completed and did not terminate early from one of the antecedent studies (X-TOLE2, X-TOLE3, or X-ACKT) are eligible to participate in X-TOLE4. Following enrollment into X-TOLE4, subjects will undergo a treatment period of up to 3 years, during which there will be a visit at 2-, 4-, and 13-weeks post-entry, with subsequent visits occurring at 13 week intervals during the first year, and then at 26-week intervals (with a telephone call in between) until dosing is completed. All subjects will be initially assigned to receive 25 mg QD of XEN1101. Subjects will be instructed to orally take XEN1101 once daily with an evening meal. Subjects will be expected to keep a daily seizure eDiary with a minimum of 80% compliance for the duration of the extension study (reporting on ≥80% of days between visits). Upon completion of dosing at the end of the treatment period, there will be an 8-week follow up period.

Official Title
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A Multicenter, Open-label, Long-term, Safety, Tolerability, and Efficacy Study of XEN1101 in Adults Diagnosed With Epilepsy

Conditions
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Focal Epilepsy, Tonic-Clonic Seizures

Intervention / Treatment
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* Drug: XEN1101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study. Subject must have successfully completed the DBP and have not terminated early from Study X-TOLE2, X-TOLE3, or X-ACKT, met all eligibility requirements, and had no important protocol deviations (in the opinion of the sponsor) or AEs (in the opinion of the investigator) that would preclude the subject's entry into the long-term extension study. In the opinion of the investigator, the subject is able to understand verbal and written instructions and will adhere to all study schedules and requirements. Subject is able to keep accurate seizure diaries. Exclusion Criteria: Subject met any of the withdrawal criteria while in Study X-TOLE2, X-TOLE3, or X-ACKT. Subject has any medical condition, personal circumstance, or ongoing AE (from Study X-TOLE2, X-TOLE3, or X-ACKT) that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study, or prevents adherence to the protocol. Subject is planning to enter a clinical study with a different investigational drug or planning to use any experimental device for treatment of epilepsy or any other medical condition during the study and until 28 days after completion of this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XEN1101 25 mg/day<br>XEN1101 25 mg/day | Drug: XEN1101<br>* XEN1101 capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The adverse events | To assess the safety and tolerability of XEN1101 | From the start of treatment in the OLE study through 8 weeks after the last dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in monthly seizure rate | Percent change in monthly seizure rate recorded at baseline (in the antecedent studies) compared to each 4-week assessment period in the treatment period in X-TOLE4. | From baseline through the active extension treatment (Week 156). | 
| Proportion of responders | Proportion of responders (subjects experiencing ≥50% reduction in seizure frequency from baseline) in each consecutive 4-week assessment period of the treatment period of the OLE study. | From baseline through the active extension treatment (Week 156). | 
| Change in Clinical Global Impression of Severity (CGI-S) | Improvement in Clinical Global Impression of Severity (CGI-S) scores over time. | From baseline through the active extension treatment (Week 156). | 
| Change in Patient Global Impression of Severity (PGI-S) | Improvement in Patient Global Impression of Severity (PGI-S) scores over time. | From baseline through the active extension treatment (Week 156). | 
| Change in Quality of Life in Epilepsy Inventory (QOLIE-31) | Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time. | From baseline through the active extension treatment (Week 156). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Seizures, Epilepsy