A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3)

May 12, 2026 updated by: Xenon Pharmaceuticals Inc.

A Randomized, Double-blind, Placebo-Controlled, Multicenter Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 as Adjunctive Therapy in Focal-Onset Seizures

The X-TOLE3 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 8-week post treatment follow-up period.

Study Type

Interventional

Enrollment (Estimated)

360

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 Contact

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1280AEB
        • Active, not recruiting
        • Hospital Britanico de Buenos Aires
      • Buenos Aires, Argentina, 1221
        • Active, not recruiting
        • Hospital Ramos Mejía
      • Buenos Aires, Argentina, 1888
        • Active, not recruiting
        • Hospital De Alta Complejidad en Red El Cruce
      • Buenos Aires, Argentina, B1832BQD
        • Active, not recruiting
        • Policlinico Lomas
      • Buenos Aires, Argentina, C1060AAF
        • Active, not recruiting
        • Instituto de Neurologia Cognitiva (INECO)
      • Buenos Aires, Argentina, C1199ABB
        • Active, not recruiting
        • Hospital Italiano
      • Buenos Aires, Argentina
        • Active, not recruiting
        • STAT Resarch S.A.
      • C.a.b.a., Argentina, C1424
        • Active, not recruiting
        • CENyR Centro de Especialidades Neurologicas y Rehabilitacion
      • C.a.b.a., Argentina, C1428DGG
        • Active, not recruiting
        • FLENI
      • Córdoba, Argentina, X5000
        • Active, not recruiting
        • Hospital Cordoba
      • San Luis, Argentina, 5701
        • Active, not recruiting
        • Hospital Central Ramon Carrilo
      • San Miguel de Tucumán, Argentina
        • Active, not recruiting
        • Sanatori del Sur S.A.
  • Australia
      • Melbourne, Australia, 3050
        • Active, not recruiting
        • Royal Melbourne Hospital
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Active, not recruiting
        • Royal Prince Alfred Hospital
      • Randwick, New South Wales, Australia, 2031
        • Active, not recruiting
        • Prince of Wales Hospital
      • Westmead, New South Wales, Australia, 2145
        • Active, not recruiting
        • Westmead Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3084
        • Active, not recruiting
        • Austin Health
      • Melbourne, Victoria, Australia, 30004
        • Active, not recruiting
        • Alfred Hospital
  • Austria
      • Innsbruck, Austria
        • Recruiting
        • University Hospital Innsbruck
      • Salzburg, Austria, 5020
        • Recruiting
        • Universitätsklinik für Neurologie
      • Vienna, Austria, 1090
        • Recruiting
        • Medical University of Vienna
  • Belgium
      • Brussels, Belgium, 1200
        • Recruiting
        • Cliniques Universitaires Saint-Luc (UCL)
      • Ghent, Belgium, 9000
        • Recruiting
        • Universitair Ziekenhuis Gent
  • Bulgaria
      • Sofia, Bulgaria, 1113
        • Active, not recruiting
        • MHATNPsy Sveti Naum EAD
      • Sofia, Bulgaria, 1172
        • Withdrawn
        • Medical center OPHTHA-NEURO
  • Chile
      • Santiago, Chile, 7620157
        • Withdrawn
        • Clínica Universidad de los Andes
      • Santiago, Chile, 8431657
        • Withdrawn
        • CINSAN
      • Santiago, Chile, 833073
        • Active, not recruiting
        • Centro de investigación Clinica UC
      • Viña del Mar, Chile
        • Active, not recruiting
        • Hospital Clinico Vina del Mar
  • Croatia
      • Osijek, Croatia, 31000
        • Withdrawn
        • University Hospital Center Osijek
      • Rijeka, Croatia, 51000
        • Withdrawn
        • Clinical Hospital Center Rijeka, Klinika za Neurologiju
      • Zagreb, Croatia, 10000
        • Recruiting
        • University hospital center Zagreb
      • Zagreb, Croatia, 10000
        • Recruiting
        • Poliklinika Bonifarm
      • Zagreb, Croatia, 1000
        • Recruiting
        • Poliklinika LF MEDICAL
  • Czechia
      • Hradec Králové, Czechia
        • Withdrawn
        • EUC Hradec Kralove Clinic
      • Prague, Czechia, 150 06
        • Recruiting
        • Nemocnicni lekarna FN Motol / Motol University Hospital
      • Prague, Czechia
        • Recruiting
        • FORBELI s.r.o.
  • Finland
      • Kuopio, Finland, 70210
        • Recruiting
        • Kuopio University Hospital
  • France
      • Bron, France, 69500
        • Recruiting
        • Hopital Neurologique Pierre Wertheimer
      • Lille, France, 59037
        • Recruiting
        • Centre Hospitalier Universitaire de Lille (CHU de Lille)
      • Paris, France, 75019
        • Recruiting
        • Hôpital Fondation A. de Rothschild
      • Paris, France, 75013
        • Recruiting
        • Hôpital de la Pitié Salpêtrière
      • Rennes, France, 35033
        • Recruiting
        • CHU de Rennes Hôpital Pontchaillou
      • Strasbourg, France, 67098
        • Recruiting
        • Hôpital de Hautepierre
  • Germany
      • Aachen, Germany, D-52074
        • Recruiting
        • Universitätsklinikum Aachen
      • Bielefeld, Germany, 33617
        • Recruiting
        • Krankenhaus Mara gGmbH
      • Frankfurt, Germany, 60528
        • Recruiting
        • University Hospital Frankfurt, ZNN - Epilepsy Center Frankfurt Rhine-Main
  • Hungary
      • Budapest, Hungary, 1145
        • Active, not recruiting
        • Semmelweis Egyetem, Idegsebészeti és Neurointervenciós Klinika
  • Israel
      • Jerusalem, Israel, 9112001
        • Recruiting
        • Hadassah Medical Center
      • Ramat Gan, Israel, 6265601
        • Recruiting
        • The Chaim Sheba Medical Center
      • Rehovot, Israel, 76100
        • Recruiting
        • Kaplan Medical Center
      • Tel Aviv, Israel, 64239
        • Recruiting
        • The Tel Aviv Sourasky Medical Center
  • Italy
      • Ancona, Italy, 60126
        • Withdrawn
        • Ospedali Riuniti di Ancona
      • Bari, Italy, 70124
        • Recruiting
        • Università degli studi di Bari Aldo Moro
  • Mexico
      • Benito Juárez, Mexico
        • Active, not recruiting
        • Grupo Medico Camino
      • Mexico City, Mexico, 14050
        • Active, not recruiting
        • Human Science Research Trials
      • Monterrey, Mexico
        • Active, not recruiting
        • Axis Heilsa S. de R.L. de C.V. Althian
      • Sinaloa, Mexico, 80020
        • Active, not recruiting
        • Neurocencias Esudios Clinicos S.C.
  • Netherlands
      • Heeze, Netherlands
        • Recruiting
        • Kempenhaeghe
  • Poland
      • Gdansk, Poland
        • Recruiting
        • COPERNICUS Podmiot Leczniczy
      • Lublin, Poland, 20-064
        • Withdrawn
        • NZOZ Neuromed M. i M. Nastaj Sp. P.
      • Nowa Sól, Poland, 67-100
        • Recruiting
        • Twoja Przychodnia Nowosolskie Centrum Medyczne
      • Warsaw, Poland, 02-172
        • Recruiting
        • MTZ Clinical Research Powered by Pratia
      • Warsaw, Poland, 02-829
        • Recruiting
        • Neurosphera Sp. z o.o.
  • Portugal
      • Coimbra, Portugal
        • Recruiting
        • Centro Hospitalar Universitário de Coimbra - CHUC
      • Guimarães, Portugal, 4835-044
        • Recruiting
        • Hospital da Senhora da Oliveira
      • Lisbon, Portugal
        • Recruiting
        • Centro Hospitalar Lisboa Ocidental
      • Lisbon, Portugal, 1649-035
        • Recruiting
        • Centro Hospitalar de Lisboa Norte
      • Porto, Portugal, 4099-001
        • Recruiting
        • Centro Hospitalar Universitário de Santo António
      • Porto, Portugal, 4464-513
        • Recruiting
        • Hospital Pedro Hispano
      • Santa Maria da Feira, Portugal, 520-211
        • Recruiting
        • Centro Hospitalar de Entre o Douro e Vouga
      • Vila Real, Portugal, 5000-508
        • Recruiting
        • ULS de Trás-os-Montes e Alto Douro
  • Spain
      • Barakaldo, Spain, 48903
        • Recruiting
        • Hospital Universitario Cruces
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Unversitario Ramon y Cajal
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • Clinical Trials, Inc.
    • California
      • Downey, California, United States, 90242
        • Recruiting
        • Rancho Research Institute
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California Los Angeles (UCLA)
      • Orange, California, United States, 92868
        • Recruiting
        • University of California Irvine Health
    • Florida
      • Gulf Breeze, Florida, United States, 32651
        • Recruiting
        • Panhandle Research and Medical Clinic
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida
    • Idaho
      • Boise, Idaho, United States, 83702
        • Recruiting
        • Consultants in Epilepsy and Neurology, PLLC
    • Illinois
      • Springfield, Illinois, United States, 62794
        • Recruiting
        • Southern Illinois University School of Medicine
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Recruiting
        • Mid-Atlantic Epilepsy and Sleep Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • 9D University Health Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Northeast Regional Epilepsy Group
    • New York
      • Woodmere, New York, United States, 11598
        • Withdrawn
        • Five Towns Neuroscience Research
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University Clinic
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
      • Columbus, Ohio, United States, 43214
        • Recruiting
        • OhioHealth
    • Oregon
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Neurological Specialities
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
    • Texas
      • Austin, Texas, United States, 78758
        • Recruiting
        • Austin Epilepsy Care Center
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Active, not recruiting
        • University of Utah Clinical Neurosciences 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 (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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). Subject must have had adequate trials of at least 2 ASMs, which were given (and tolerated) at adequate therapeutic doses, without achieving sustained seizure freedom.
  • 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 only, non-epileptic psychogenic seizure, primary generalized seizure, developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
  • 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.
  • History of status epilepticus or repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
  • History of neurosurgery for seizures <1 year prior to Visit 1, or radiosurgery <2 years prior to enrollment.
  • 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.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Placebo Capsules
Experimental: XEN1101 25 mg/day
Drug: XEN1101
XEN1101 Capsules
Other Names:
  • Azetukalner
Experimental: XEN1101 15 mg/day
Drug: XEN1101
XEN1101 Capsules
Other Names:
  • Azetukalner

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Median percent change (MPC) in focal seizure frequency from baseline to DBP for XEN1101 versus placebo.
Time Frame: From baseline through to the double blind period (week 12).
From baseline through to the double blind period (week 12).

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of subjects experiencing ≥50% reduction in focal seizure frequency from baseline through the DBP for XEN1101 versus placebo.
Time Frame: From baseline through to the double blind period (week 12).
From baseline through to the double blind period (week 12).
MPC in weekly (7 days) focal seizure frequency from baseline to Week 1 for XEN1101 versus placebo.
Time Frame: From baseline through to the week 1.
From baseline through to the week 1.
Proportion of subjects experiencing "at least much improved" (including "much" and "very much improved") in Patient Global Impression of Change (PGI-C).
Time Frame: From baseline through to the double blind period (week 12).
From baseline through to the double blind period (week 12).
To assess adverse events as criteria for safety and tolerability of XEN1101.
Time Frame: From screening through to 56 days post-final dose
From screening through to 56 days post-final dose

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: Xenon 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)

May 9, 2023

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

January 26, 2023

First Submitted That Met QC Criteria

February 6, 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-010-302
  • 2022-502281-25-00 (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

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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