A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE2)

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-TOLE2 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

Completed

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 (Actual)

380

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, C1023AAB
        • Stat Research S.A.
      • Buenos Aires, Argentina, 1060
        • INECO and Favoloro Fundation
      • Buenos Aires, Argentina, 1221
        • Hospital General de Agudos J.M. Ramos Mejia
      • Buenos Aires, Argentina, B1888AAE
        • Hospital De Alta Complejidad en Red el Cruce Nestor Kirchner - SAMIC
      • Buenos Aires, Argentina, C1199ABB
        • Hospital Italiano
      • Caba, Argentina, C1424
        • CENyR
      • Córdoba, Argentina, CP 5000
        • Hospital Cordoba
      • San Miguel de Tucumán, Argentina, 4000
        • Sanatorio del Sur S.A.
  • Australia
      • Melbourne, Australia, 3052
        • The Royal Melbourne Hospital
    • Melbourne
      • Fitzroy, Melbourne, Australia, 3065
        • St Vincent's Hospital Melbourne
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital (RAPH)
      • Sydney, New South Wales, Australia, 2031
        • Prince of Wales Hospital
      • Sydney, New South Wales, Australia, 2217
        • Southern Neurology
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Queensland
      • Brisbane, Queensland, Australia, 4101
        • The University of Queensland (UQ) - Mater Research Institute (MRI)
    • Victoria
      • Heidelberg, Victoria, Australia, 3079
        • Austin Health Pharmacy Clinical Trials
      • Melbourne, Victoria, Australia, 3004
        • The Alfred Hospital (Alfred Health)
  • Bulgaria
      • Blagoevgrad, Bulgaria, 2700
        • MHAT Puls AD
  • Canada
    • Alberta
      • Lethbridge, Alberta, Canada, T1J 0N9
        • Center for Neurologic Research
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • London Health Sciences Centre
    • Quebec
      • Montreal, Quebec, Canada, H2X3E4
        • Le Centre Hospitalier de l'Universite' de Montreal (CHUM)
  • Chile
      • Santiago, Chile, 833073
        • Centro de investigación Clinica UC
      • Viña del Mar, Chile, 2520612
        • Hospital Clinico Viña del Mar
  • Czechia
      • Prague, Czechia, 160-00
        • FORBELI s.r.o., Neurologicka ambulance
  • Georgia
      • Tbilisi, Georgia, 0186
        • Institute of Neurology and Neuropsychology
      • Tbilisi, Georgia, 0121
        • American Hospital Network LLC
  • Germany
      • Bielefeld, Germany, 33617
        • Epilepsy Center Bethel
      • Bonn, Germany
        • Universitätsklinikum Bonn
      • Frankfurt, Germany, 60528
        • Epilepsiezentrum Frankfurt Rhein-Main
      • Freiburg im Breisgau, Germany, 79106
        • University Medical Center Freiburg
      • Marburg, Germany, 35043
        • Philipps-Universität Marburg
      • Munich, Germany, 81277
        • LMU Munich, Department of Neurology
      • Tübingen, Germany, 72076
        • Universitatsklinikum Tubingen
      • Ulm, Germany, 89081
        • Universitatsklinik fur neurologie, universitats - und Rehabilitationskliniken Ulm
  • Ireland
      • Dublin, Ireland, D09 YD60
        • Beaumont Hospital
  • Italy
      • Bologna, Italy, 40139
        • Istituto delle Scienze Neurologiche di Bologna
      • Pescara, Italy, 66100
        • Università Degli Studi Gabriele d'Annunzio Di Chieti
      • Pisa, Italy, 56100
        • Azienda Ospedaliero Universitaria Pisana
      • Rome, Italy, 00186
        • Azienda Ospedaliero-Universitaria Policlinico Umberto I
  • Latvia
      • Riga, Latvia, LV-1002
        • Pauls Stradina Clinical university hospital
      • Riga, Latvia, LV-1024
        • Riga East University Hospital
  • Mexico
      • Mexico City, Mexico, 14050
        • Human Science Research Trials S. de R.L. de C.V.
      • Sinaloa, Mexico, 80020
        • Neurocencias Esudios Clinicos SC
  • New Zealand
      • Auckland, New Zealand, 1023
        • University of Auckland
      • Hamilton, New Zealand, 3204
        • Waikato Hospital
  • Poland
      • Bydgoszcz, Poland, 85-163
        • Centrum Medyczne Neuromed
      • Katowice, Poland, 40-650
        • Nzoz Novo-Med
      • Nowa Sól, Poland, 67-100
        • Twoja Przychodnia NCM
      • Warsaw, Poland, 02-829
        • Neurosphera Sp. z o.o.
  • Portugal
      • Porto, Portugal, 4200-450
        • Unidade Local de Saúde de São João
      • Porto, Portugal, 4464-513
        • Hospital Pedro Hispano
      • Santa Maria da Feira, Portugal, 4520-220
        • Centro Hospitalar de Entre o Douro e Vouga
  • Spain
      • Barcelona, Spain, 08036
        • Unitat d'Assaigs Clínics. Servei de Farmàcia
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal
      • Madrid, Spain, 28034
        • Hospital Ruber Internacional
      • Madrid, Spain, 28034
        • Hospital Vithas La Milagrosa
      • Madrid, Spain, 28040
        • IIS-Fundacion Jimenez Diaz/Farmacia
      • Málaga, Spain, 29010
        • Hospital Regional de Malaga
      • Valencia, Spain, 46026
        • Hospital Universitario y Politécnico La Fe
      • Valladolid, Spain, 47003
        • Hospital Clinico Universitario Valladolid
  • United Kingdom
      • Birmingham, United Kingdom, B152GW
        • University Hospitals Birmingham NHS Foundation Trust
      • Cardiff, United Kingdom, CF144XW
        • University Hospital of Wales
      • Leeds, United Kingdom, LS1 3EX
        • Leeds Teaching Hospitals NHS Trust
      • London, United Kingdom, WC1N 3HR
        • Royal London Hospital for Integrated Medicine
      • London, United Kingdom, SW17 0QT
        • St. George's Hospital NHS Foundation Trust
      • Oxford, United Kingdom, OX3 9DU
        • John Radcliffe Hospital
      • Salford, United Kingdom, M6 8HD
        • Northern Care Alliance NHS Foundation Trust, Salford Care Organisation
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36604
        • Strada Patient Care Center
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • Xenoscience
      • Tucson, Arizona, United States, 85724
        • University of Arizona, Health Sciences Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Clinical Trials, Inc
    • California
      • Los Angeles, California, United States, 90025
        • Brain Science Research Institute
      • Sacramento, California, United States, 95817
        • University of California, David Clinical & Translational Science Center Clinical Research (CCRC)
    • Colorado
      • Aurora, Colorado, United States, 80011
        • Anschutz Health Sciences
    • Florida
      • Miami, Florida, United States, 33176
        • Serenity Research
      • Orlando, Florida, United States, 32806
        • Research Institute of Orlando, LLC
      • Pensacola, Florida, United States, 32503
        • Panhandle Research & Medical Clinic
      • Port Charlotte, Florida, United States, 33952
        • Medsol Clinical Research Center
      • Tampa, Florida, United States, 33606
        • University of South Florida
      • Weston, Florida, United States, 33021
        • Encore Medical Research of Weston, LLC
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Emory Brain Health Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96817
        • Hawaii Pacific Neuroscience
    • Idaho
      • Boise, Idaho, United States, 83702
        • Consultants in Epilepsy and Neurology
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University, IU Health Partners, Adult Neurology Clinic
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • The University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • Bluegrass Epilepsy Research, LLC
      • Lexington, Kentucky, United States, 40536-0284
        • University of Kentucky, Dept. of Neurology
    • Maine
      • Scarborough, Maine, United States, 04074
        • MaineHealth Neurology - Scarborough
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
      • Baltimore, Maryland, United States, 21237
        • MedStar Franklin Square Medical Center
      • Bethesda, Maryland, United States, 20817
        • Mid-Atlantic Epilepsy and Sleep Center
      • Clinton, Maryland, United States, 20735
        • MedStar Georgetown University Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • East Lansing, Michigan, United States, 48824
        • Michigan State University
      • Grand Rapids, Michigan, United States, 49506
        • Cornwell Health
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Minneapolis Clinic of Neurology
    • Missouri
      • St Louis, Missouri, United States, 63104
        • Saint Louis University Medical School - Neurosciences Clinical Research Unit
      • St Louis, Missouri, United States, 63110
        • Washington University, St. Louis
    • 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, 10029
        • Mount Sinai Medical Center
      • New York, New York, United States, 10016
        • NYU Comprehensive Epilepsy Center (CEC)
      • New York, New York, United States, 10021
        • Weill Cornell Medicine/ New York-Presbyterian Hospital
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
      • The Bronx, New York, United States, 10467-2401
        • Montefiore Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28211
        • Onsite Clinical Solutions, LLC
      • Durham, North Carolina, United States, 27713
        • Duke Neurology
      • Raleigh, North Carolina, United States, 27607
        • Meridian Clinical Research, LLC
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Health
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Health
    • Oregon
      • Portland, Oregon, United States, 97225
        • Providence Brain & Spine Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Philadelphia, Pennsylvania, United States, 19140-4105
        • Temple University Hospital
    • Texas
      • Austin, Texas, United States, 78758
        • Austin Epilepsy Care Center (AECC)
      • El Paso, Texas, United States, 79912
        • ANESC Research
      • Houston, Texas, United States, 77030
        • UT Physicians Epilepsy Clinic
      • San Antonio, Texas, United States, 78229
        • UT Health San Antonio
    • Virginia
      • Roanoke, Virginia, United States, 24013
        • Carilion Clinic - Neurology
      • Virginia Beach, Virginia, United States, 23456
        • Sentara Neurology Specialists
    • Washington
      • Seattle, Washington, United States, 98104
        • 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 to 75 years (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 monthly (28 days) 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 monthly (28 days) 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: 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)

November 18, 2022

Primary Completion (Actual)

January 12, 2026

Study Completion (Actual)

February 3, 2026

Study Registration Dates

First Submitted

November 6, 2022

First Submitted That Met QC Criteria

November 6, 2022

First Posted (Actual)

November 14, 2022

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-010-301
  • 2022-502000-73-00 (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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