Focal Epilepsy, Tonic-Clonic Seizures
Conditions
Keywords
Epilepsy, Seizures
Brief summary
This study will evaluate the long term safety, tolerability, pharmacokinetics (PK), and efficacy of XEN1101 in subjects with Focal Onset Seizures (FOS) or Primary Generalized Tonic-Clonic Seizures (PGTCS) for the treatment of seizures for up to 6 years.
Detailed description
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 in subjects with FOS or PGTCS for the treatment of seizures for up to 6 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 6 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. Subjects will be initially assigned to XEN1101 as follows: * 25 mg QD for subjects aged ≥18 years * For subjects aged ≥12 and \<18 years * 15 mg QD for those * who weigh \<45 kg at the start of the X-TOLE4 study * who weighed \<45 kg during the X-ACKT study * who weighed ≥45 kg at randomization in the X-ACKT study and had dose reduction(s) for intolerability * 25 mg QD for all others Subjects will be instructed to orally take XEN1101 once daily (QD) 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.
Interventions
DRUGXEN1101
XEN1101 capsules
Sponsors
Xenon Pharmaceuticals Inc.
Worldwide Clinical Trials
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must be properly informed of the nature and risks of the study and give informed consent in writing prior to entering the study (for adult subjects) and for adolescent subject's parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study. 2. Subject must have successfully completed the double-blind treatment period (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 adverse events (AEs) (in the opinion of the investigator) that would preclude the subject's entry into the long-term extension study. 3. 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. 4. Subject is able to keep accurate seizure diaries.
Exclusion criteria
1. Subject met any of the withdrawal criteria while in Study X-TOLE2, X-TOLE3, or X-ACKT. 2. 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. 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The adverse events | From the start of treatment in the open-label extension (OLE) study through 8 weeks after the last dose. | To assess the safety and tolerability of XEN1101 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in monthly seizure rate | From baseline through the active extension treatment (Week 312). | 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. |
| Proportion of responders | From baseline through the active extension treatment (Week 312). | 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. |
| Change in Clinical Global Impression of Severity (CGI-S) | From baseline through the active extension treatment (Week 312). | Improvement in Clinical Global Impression of Severity (CGI-S) scores over time. |
| Change in Patient Global Impression of Severity (PGI-S) | From baseline through the active extension treatment (Week 312). | Improvement in Patient Global Impression of Severity (PGI-S) scores over time. |
| Change in Quality of Life in Epilepsy Inventory (QOLIE-31) | From baseline through the active extension treatment (Week 312). | Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time. |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Chile, Croatia, Czechia, Finland, France, Georgia, Germany, Hungary, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Poland, Portugal, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Xenon Pharmaceuticals Inc.
Outcome results
None listed