An Open-label Study of XEN1101 in Epilepsy (X-TOLE4)

May 12, 2026 updated by: Xenon Pharmaceuticals Inc.

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

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

880

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1280AEB
        • Hospital Britanico de Buenos Aires
      • Buenos Aires, Argentina, C1199ABB
        • Hospital Italiano de Buenos Aires
      • Buenos Aires, Argentina, C1023AAB
        • Stat Research S.A.
      • Buenos Aires, Argentina, 1221
        • Hospital General de Agudos "José M. Ramos Mejía"
      • Buenos Aires, Argentina, C1428DGG
        • FLENI (Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia)
      • Buenos Aires, Argentina, B1832BQD
        • Asociacion Medica de Lomas de Zamora S.A. - Policlinicio Lomas
      • Buenos Aires, Argentina, C1424BYD
        • CENyR, Centro de Especialidades Neurologicas u Rehabilitacion
      • Buenos Aires, Argentina, C1060AAF
        • Centro de Psicología Médica San Martín de Tours SRL (CITES-INECO)
      • Córdoba, Argentina, X5000
        • Hospital Cordoba
      • San Juan Bautista, Argentina, 1888
        • Hospital De Alta Complejidad en Red El Cruce - Dr Nester Carlos Kirchner Servicio de Atencion Medica Integral Para la Communidad
      • San Luis, Argentina, 5701
        • Hospital Central Ramon Carrillo
      • San Miguel de Tucumán, Argentina, 4000
        • Sanatorio del Sur S.A.
  • Australia
      • Camperdown, Australia, 2050
        • Royal Prince Alfred Hospital
      • Fitzroy, Australia, 3065
        • St Vincent's Hospital Melbourne
      • Heidelberg, Australia, 3084
        • Austin Health Pharmacy Clinical Trials
      • Kogarah, Australia, 2217
        • Southern Neurology
      • Melbourne, Australia, 30004
        • Alfred Hospital Neurology CT Dept of Neuroscience
      • Parkville, Australia, 3050
        • The Royal Melbourne Hospital
      • South Brisbane, Australia, 4101
        • Mater Misericordiae Ltd South Brisbane
      • Westmead, Australia, 2145
        • Westmead Hospital Dept. of Neurology Epilepsy Unit
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Prince of Wales Hospital
  • Austria
      • Innsbruck, Austria, 6020
        • University Hospital Innsbruck
      • Vienna, Austria, 1090
        • Universitätsklinik für Neurologie, Medizinische Universität Wien
  • Belgium
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-Luc (UCL)
      • Ghent, Belgium, 9000
        • Universitair Ziekenhuis Gent
  • Bulgaria
      • Blagoevgrad, Bulgaria, 2700
        • Hospital for active treatmnt Puls AD Neurology Dpt
      • Sofia, Bulgaria, 1113
        • MHATNP St. Naum
  • Canada
      • Montreal, Canada, H2X 0C1
        • Le Centre Hospitalier de l'Universite' de Montreal (CHUM)
    • Alberta
      • Lethbridge, Alberta, Canada, T1J 0N9
        • Center for Neurologic Research
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • London Health Sciences Center
  • Chile
      • Santiago, Chile, 8330073
        • Centro de investigación Clinica UC
      • Viña del Mar, Chile, 2520612
        • Hospital Clinico Vina del Mar
  • Croatia
      • Zagreb, Croatia, 10000
        • University Hospital Centre Zagreb
      • Zagreb, Croatia, 10000
        • Poliklinika Bonifarm
      • Zagreb, Croatia, 10000
        • Altavita Centar j.d.o.o.
  • Czechia
      • Prague, Czechia, 160 00
        • FORBELI s.r.o.
      • Prague, Czechia, 150 06
        • Motol University Hospital
  • Finland
      • Kuopio, Finland, 70 210
        • Kuopio University Hospital
  • France
      • Lyon, France, 69003
        • Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
      • Paris, France, 75013
        • Hôpitaux Universitaires Pitié Salpêtrière
      • Paris, France, 75010
        • Hôpital Fondation Adolphe de Rothschild
      • Rennes, France, 35033
        • CHU de Rennes - Hopital Pontchaillou
      • Strasbourg, France, 67200
        • Hopital de Hautepierre
  • Georgia
      • Tbilisi, Georgia, 0102
        • American Hospital Network LLC
      • Tbilisi, Georgia, 0186
        • Institute of Neurology and Neuropsychology
  • Germany
      • Aachen, Germany, 52074
        • Universitätsklinikum Aachen
      • Bielefeld, Germany, 33617
        • Krankenhaus Mara gGmbH
      • Frankfurt, Germany, 60528
        • Universitätsklinikum, ZNN - Epilepsiezentrum Frankfurt Rhein-Main
      • Freiburg im Breisgau, Germany, 79106
        • University Hospital Freiburg
      • Marburg, Germany, 35043
        • Philipps-Universität Marburg
      • München, Germany, 81377
        • Klinikum der Universität München
      • Ulm, Germany, 89081
        • Universitaets-Und Rehabilitations Ulm (RKU)
  • Hungary
      • Budapest, Hungary, 1145
        • Semmelweis Egyetem, Idegsebészeti és Neurointervenciós Klinika
  • Ireland
      • Dublin, Ireland, NO9 V2NO
        • Beaumont Hospital
  • Israel
      • Jerusalem, Israel, 9112001
        • Hadassah Medical Center (HMC)
      • Rehovot, Israel, 76100
        • Kaplan Medical Center (KMC)
      • Tel Aviv, Israel, 6423906
        • The Tel Aviv Sourasky Medical Center
  • Italy
      • Bologna, Italy, 40139
        • IRCCS Istituto delle Scienze Neurologiche Bologna
      • Chieti, Italy, 66100
        • Universita' Degli Studi Gabriele d'Annunzio Di Chieti
      • Pisa, Italy, 56126
        • Azienda Ospedaliero Universitaria Pisana
      • Roma, Italy, 00185
        • Azienda Ospedaliero Universitaria Policlinico Umberto I
  • Mexico
      • Mexico City, Mexico, 3310
        • Grupo Medico Camino Sc
      • Mexico City, Mexico, 14050
        • Human Science Research Trials
      • Sinaloa, Mexico
        • Neurociencias Estudios Clínicos SC
  • New Zealand
      • Auckland, New Zealand, 1023
        • University of Auckland
      • Hamilton, New Zealand, 3204
        • Waikato Hospital
  • Poland
      • Bydgoszcz, Poland, 85-163
        • Centrum Medyczne Neuromed
      • Gdansk, Poland, 80-803
        • COPERNICUS Podmiot Leczniczy Sp. z o.o.
      • Lublin, Poland, 20-064
        • NZOZ Neuromed M. i M.
      • Nowa Sól, Poland, 67-100
        • Twoja Przychodnia Nowosolskie Centrum Medyczne
      • Warsaw, Poland, 02-172
        • MTZ Clinical Research Powered by Pratia
      • Warsaw, Poland, 03-829
        • Neurosphera Sp z o.o.
  • Portugal
      • Coimbra, Portugal, 3000-075
        • Centro Hospitalar Universitário de Coimbra (CHUC)
      • Guimarães, Portugal, 4835-044
        • Hospital Senhora da Oliviera de Guimaraes
      • Lisbon, Portugal, 1349-019
        • Centro Hospitalar Lisboa Ocidental, EPE - Hospital Egas Moniz
      • Porto, Portugal, 4200-319
        • Unidade Local de Saúde de São João
      • Porto, Portugal, 4464-513
        • Unidade Local Saúde Matosinhos
      • Porto, Portugal, 4050-342
        • Centro Hospitalar Universitario de Santo António, E.P.E
      • Santa Maria da Feira, Portugal, 520-211
        • Centro Hospitalar de Entre o Douro e Vouga
  • Spain
      • Barakaldo, Spain, 48903
        • Hospital Universitario Cruces
      • Barcelona, Spain, 08035
        • Vall d'Hebron Hospital
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28040
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal
      • Madrid, Spain, 28034
        • Hospital Ruber Internacional
      • Madrid, Spain, 28010
        • Hospital Vithas La Milagrosa
      • Málaga, Spain, 29010
        • Hospital Regional de Malaga
      • Valencia, Spain, 46026
        • Hospital la Fé
      • Valladolid, Spain, 47003
        • Hospital Clinico Universitario de Valladolid
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Queen Elizabeth Hospital Birmingham
      • London, United Kingdom, WC1N 3BG
        • University College London
      • London, United Kingdom, SW17 0RE
        • St George's Hospital NHS Foundation Trust
      • Oxford, United Kingdom, OX39DU
        • John Radcliffe Hospital
      • Salford, United Kingdom, M6 8HD
        • Salford Royal NHS Foundation Trust - Greater Manchester Neuroscience Centre (GMNC)
    • England
      • Leeds, England, United Kingdom, LS97TF
        • Leeds Teaching Hospitals NHS Trust
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 4XW
        • Cardiff and Vale UHB
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • Xenoscience
      • Tucson, Arizona, United States, 85724
        • University of Arizona - Health Sciences
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Clinical Trials, Inc
    • California
      • Los Angeles, California, United States, 90025
        • Brain Science Research Institute
      • Orange, California, United States, 92868
        • UC Irvine Health
      • Sacramento, California, United States, 95817
        • University of California, Davis Clinical & Translational Science Center Clinical Research (CCRC)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital Anschutz Outpatient Pavilion
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Florida
      • Miami, Florida, United States, 33176
        • Serenity Research Center, LLC
      • Orlando, Florida, United States, 32806
        • Research Institute of Orlando, LLC
      • Pensacola, Florida, United States, 10021
        • Panhandle Research & Medical Clinic
      • Tampa, Florida, United States, 33606
        • University of South Florida
      • Weston, Florida, United States, 33331
        • Encore Medical Research of Weston, LLC
    • Hawaii
      • Honolulu, Hawaii, United States, 96817
        • Hawaii Pacific Neuroscience
    • Idaho
      • Boise, Idaho, United States, 83704
        • Consultants in Epilepsy and Neurology
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine
    • Kansas
      • Kansas City, Kansas, United States, 66103
        • The University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • Bluegrass Epilepsy Research, LLC
      • Lexington, Kentucky, United States, 40536
        • Kentucky Clinic
    • Maine
      • Scarborough, Maine, United States, 04074
        • MMP Neurology
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
      • Bethesda, Maryland, United States, 20817
        • Mid-Atlantic Epilepsy and Sleep Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Worcester, Massachusetts, United States, 06155
        • UMass Chan Medical School
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-2435
        • University of Michigan Hospitals
      • Detroit, Michigan, United States, 48201
        • Wayne State University
      • East Lansing, Michigan, United States, 48824
        • Michigan State University
      • Grand Rapids, Michigan, United States, 49503
        • Cornwell Health (Spectrum Health Hospitals)
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Minneapolis Clinic of Neurology
    • Missouri
      • St Louis, Missouri, United States, 63104
        • Saint Louis University Medical School
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Northeast Epilepsy Group
    • New York
      • Buffalo, New York, United States, 14226
        • Dent Neurosciences Research Center
      • New York, New York, United States, 10016
        • New York University Comprehensive Epilepsy Center
      • New York, New York, United States, 10029
        • Mount Sinai Health
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
      • The Bronx, New York, United States, 10467
        • Montefiiore Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28211
        • Onsite Clinical Solutions
      • Durham, North Carolina, United States, 27710
        • Duke University
      • Raleigh, North Carolina, United States, 27607
        • Meridian Clinical Research, LLC
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Health
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Brain and Spine Hospital
    • Oregon
      • Portland, Oregon, United States, 97225
        • Providence Neurological Specialities
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Austin, Texas, United States, 78758
        • Austin Epilepsy Care Center
      • El Paso, Texas, United States, 79912
        • ANESC Research
      • San Antonio, Texas, United States, 78229
        • UT Health San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Clinical Neurosciences Center
    • Virginia
      • Roanoke, Virginia, United States, 24013
        • Carilion Clinic
      • Virginia Beach, Virginia, United States, 23456
        • Sentara Neurology Specialists
    • Washington
      • Seattle, Washington, United States, 10012
        • University of Washington Main Hospital
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora St. Luke's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: XEN1101 15 or 25 mg/day
Drug: XEN1101
XEN1101 capsules
Other Names:
  • Azetukalner

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The adverse events
Time Frame: 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
From the start of treatment in the open-label extension (OLE) study through 8 weeks after the last dose.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in monthly seizure rate
Time Frame: 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.
From baseline through the active extension treatment (Week 312).
Proportion of responders
Time Frame: 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.
From baseline through the active extension treatment (Week 312).
Change in Clinical Global Impression of Severity (CGI-S)
Time Frame: From baseline through the active extension treatment (Week 312).
Improvement in Clinical Global Impression of Severity (CGI-S) scores over time.
From baseline through the active extension treatment (Week 312).
Change in Patient Global Impression of Severity (PGI-S)
Time Frame: From baseline through the active extension treatment (Week 312).
Improvement in Patient Global Impression of Severity (PGI-S) scores over time.
From baseline through the active extension treatment (Week 312).
Change in Quality of Life in Epilepsy Inventory (QOLIE-31)
Time Frame: From baseline through the active extension treatment (Week 312).
Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time.
From baseline through the active extension treatment (Week 312).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xenon Pharmaceuticals Inc.

Collaborators

Worldwide Clinical Trials

Investigators

  • Study Director: Medical Director, Xenon Pharmaceuticals Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 25, 2023

Primary Completion (Estimated)

April 1, 2033

Study Completion (Estimated)

June 1, 2033

Study Registration Dates

First Submitted

January 13, 2023

First Submitted That Met QC Criteria

February 7, 2023

First Posted (Actual)

February 8, 2023

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XPF-010-304
  • 2022-502282-24-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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