An Open-label Study of XEN1101 in Epilepsy

Phase 3Enrolling By InvitationNCT05718817

Xenon Pharmaceuticals Inc.880 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

880

Conditions

Focal Epilepsy Tonic-Clonic Seizures

Interventions

XEN1101DRUG

XEN1101 capsules

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Locations (152)

Outcomes

Primary Outcomes

The adverse events

To assess the safety and tolerability of XEN1101

Time frame: From the start of treatment in the open-label extension (OLE) study through 8 weeks after the last dose.

Secondary Outcomes

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.