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Focal EpilepsyPhase 3X-TOLE4NCT05718817

An Open-label Study of XEN1101 in Epilepsy

A Phase 3 study testing XEN1101 in people with Focal Epilepsy and Tonic-Clonic Seizures, run by Xenon Pharmaceuticals Inc. at 152 sites in 25 countries.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Focal Epilepsy, Tonic-Clonic Seizures
What is being tested?
XEN1101
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
880 participants
Where
152 sitesin 25 countries
Study dates
25 Apr 2023to Jun 2033
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • 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.
  • Subject is able to keep accurate seizure diaries.

Who cannot join

  • Subject met any of the withdrawal criteria while in Study X-TOLE2, X-TOLE3, or X-ACKT.
  • 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.
  • 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.

Trial locations and contacts

152 sites in 25 countries. Contact the study team or a site near you to ask about taking part.

152 sites in 25 countries

United States54 sites

  • Summa Health

    Akron, Ohio, 44304

  • University of Michigan Hospitals

    Ann Arbor, Michigan, 48109-2435

  • University of Colorado Hospital Anschutz Outpatient Pavilion

    Aurora, Colorado, 80045

  • Austin Epilepsy Care Center

    Austin, Texas, 78758

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Mid-Atlantic Epilepsy and Sleep Center

    Bethesda, Maryland, 20817

  • Consultants in Epilepsy and Neurology

    Boise, Idaho, 83704

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dent Neurosciences Research Center

    Buffalo, New York, 14226

  • Minneapolis Clinic of Neurology

    Burnsville, Minnesota, 55337

  • Onsite Clinical Solutions

    Charlotte, North Carolina, 28211

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • The Ohio State University Brain and Spine Hospital

    Columbus, Ohio, 43210

  • Wayne State University

    Detroit, Michigan, 48201

  • Duke University

    Durham, North Carolina, 27710

  • Michigan State University

    East Lansing, Michigan, 48824

  • ANESC Research

    El Paso, Texas, 79912

  • Cornwell Health (Spectrum Health Hospitals)

    Grand Rapids, Michigan, 49503

  • Northeast Epilepsy Group

    Hackensack, New Jersey, 07601

  • Hawaii Pacific Neuroscience

    Honolulu, Hawaii, 96817

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • The University of Kansas Medical Center

    Kansas City, Kansas, 66103

  • Bluegrass Epilepsy Research, LLC

    Lexington, Kentucky, 40504

  • Kentucky Clinic

    Lexington, Kentucky, 40536

  • Clinical Trials, Inc

    Little Rock, Arkansas, 72205

  • Brain Science Research Institute

    Los Angeles, California, 90025

  • Serenity Research Center, LLC

    Miami, Florida, 33176

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • New York University Comprehensive Epilepsy Center

    New York, New York, 10016

  • Mount Sinai Health

    New York, New York, 10029

  • UC Irvine Health

    Orange, California, 92868

  • Research Institute of Orlando, LLC

    Orlando, Florida, 32806

  • Panhandle Research & Medical Clinic

    Pensacola, Florida, 10021

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Xenoscience

    Phoenix, Arizona, 85004

  • Providence Neurological Specialities

    Portland, Oregon, 97225

  • Meridian Clinical Research, LLC

    Raleigh, North Carolina, 27607

  • Carilion Clinic

    Roanoke, Virginia, 24013

  • University of California, Davis Clinical & Translational Science Center Clinical Research (CCRC)

    Sacramento, California, 95817

  • University of Utah Clinical Neurosciences Center

    Salt Lake City, Utah, 84132

  • UT Health San Antonio

    San Antonio, Texas, 78229

  • MMP Neurology

    Scarborough, Maine, 04074

  • University of Washington Main Hospital

    Seattle, Washington, 10012

  • Saint Louis University Medical School

    St Louis, Missouri, 63104

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • University of South Florida

    Tampa, Florida, 33606

  • Montefiiore Medical Center

    The Bronx, New York, 10467

  • University of Arizona - Health Sciences

    Tucson, Arizona, 85724

  • Sentara Neurology Specialists

    Virginia Beach, Virginia, 23456

  • Encore Medical Research of Weston, LLC

    Weston, Florida, 33331

  • UMass Chan Medical School

    Worcester, Massachusetts, 06155

Other trials in United States

Argentina12 sites

  • Hospital General de Agudos "José M. Ramos Mejía"

    Buenos Aires, 1221

  • Asociacion Medica de Lomas de Zamora S.A. - Policlinicio Lomas

    Buenos Aires, B1832BQD

  • STAT Research S.A.

    Buenos Aires, C1023AAB

  • Centro de Psicología Médica San Martín de Tours SRL (CITES-INECO)

    Buenos Aires, C1060AAF

  • Hospital Italiano de Buenos Aires

    Buenos Aires, C1199ABB

  • Hospital Britanico de Buenos Aires

    Buenos Aires, C1280AEB

  • CENyR, Centro de Especialidades Neurologicas u Rehabilitacion

    Buenos Aires, C1424BYD

  • FLENI (Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia)

    Buenos Aires, C1428DGG

  • Hospital Córdoba

    Córdoba, X5000

  • Hospital De Alta Complejidad en Red El Cruce - Dr Nester Carlos Kirchner Servicio de Atencion Medica Integral Para la Communidad

    San Juan Bautista, 1888

  • Hospital Central Ramon Carrillo

    San Luis, 5701

  • Sanatorio del SUR S.A.

    San Miguel de Tucumán, 4000

Other trials in Argentina

Spain10 sites

  • Hospital Universitario Cruces

    Barakaldo, 48903

  • Vall d'Hebron Hospital

    Barcelona, 08035

  • Hospital Vithas La Milagrosa

    Madrid, 28010

  • Hospital Ramón Y Cajal

    Madrid, 28034

  • Hospital Ruber Internacional

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Regional De Malaga

    Málaga, 29010

  • Hospital La Fe

    Valencia, 46026

  • Hospital Clinico Universitario de Valladolid

    Valladolid, 47003

Other trials in Spain

Australia9 sites

  • Royal Prince Alfred Hospital

    Camperdown, 2050

  • St Vincent's Hospital Melbourne

    Fitzroy, 3065

  • Austin Health Pharmacy Clinical Trials

    Heidelberg, 3084

  • Southern Neurology

    Kogarah, 2217

  • Alfred Hospital Neurology CT Dept of Neuroscience

    Melbourne, 30004

  • The Royal Melbourne Hospital

    Parkville, 3050

  • Prince of Wales Hospital

    Randwick, New South Wales, 2031

  • Mater Misericordiae Ltd South Brisbane

    South Brisbane, 4101

  • Westmead Hospital Dept. of Neurology Epilepsy Unit

    Westmead, 2145

Other trials in Australia

Germany7 sites

  • Universitätsklinikum Aachen

    Aachen, 52074

  • Krankenhaus Mara gGmbH

    Bielefeld, 33617

  • Universitätsklinikum, ZNN - Epilepsiezentrum Frankfurt Rhein-Main

    Frankfurt, 60528

  • University Hospital Freiburg

    Freiburg im Breisgau, 79106

  • Philipps-Universität Marburg

    Marburg, 35043

  • Klinikum der Universität München

    München, 81377

  • Universitaets-Und Rehabilitations Ulm (RKU)

    Ulm, 89081

Other trials in Germany

Portugal7 sites

  • Centro Hospitalar Universitário de Coimbra (CHUC)

    Coimbra, 3000-075

  • Hospital Senhora da Oliviera de Guimaraes

    Guimarães, 4835-044

  • Centro Hospitalar Lisboa Ocidental, EPE - Hospital Egas Moniz

    Lisbon, 1349-019

  • Centro Hospitalar Universitario de Santo António, E.P.E

    Porto, 4050-342

  • Unidade Local de Saúde de São João

    Porto, 4200-319

  • Unidade Local Saúde Matosinhos

    Porto, 4464-513

  • Centro Hospitalar de Entre o Douro e Vouga

    Santa Maria da Feira, 520-211

Other trials in Portugal

United Kingdom7 sites

  • Queen Elizabeth Hospital Birmingham

    Birmingham, B15 2TH

  • Cardiff and Vale UHB

    Cardiff, Wales, CF14 4XW

  • Leeds Teaching Hospitals NHS Trust

    Leeds, England, LS97TF

  • St George's Hospital NHS Foundation Trust

    London, SW17 0RE

  • University College London

    London, WC1N 3BG

  • John Radcliffe Hospital

    Oxford, OX39DU

  • Salford Royal NHS Foundation Trust - Greater Manchester Neuroscience Centre (GMNC)

    Salford, M6 8HD

Other trials in United Kingdom

Poland6 sites

  • Centrum Medyczne Neuromed

    Bydgoszcz, 85-163

  • COPERNICUS Podmiot Leczniczy Sp. z o.o.

    Gdansk, 80-803

  • NZOZ Neuromed M. i M.

    Lublin, 20-064

  • Twoja Przychodnia Nowosolskie Centrum Medyczne

    Nowa Sól, 67-100

  • MTZ Clinical Research Powered by Pratia

    Warsaw, 02-172

  • Neurosphera Sp z o.o.

    Warsaw, 03-829

Other trials in Poland

France5 sites

  • Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon

    Lyon, 69003

  • Hôpital Fondation Adolphe de Rothschild

    Paris, 75010

  • Hôpitaux Universitaires Pitié Salpêtrière

    Paris, 75013

  • CHU De Rennes - Hôpital Pontchaillou

    Rennes, 35033

  • Hôpital de Hautepierre

    Strasbourg, 67200

Other trials in France

Italy4 sites

  • IRCCS Istituto delle Scienze Neurologiche Bologna

    Bologna, 40139

  • Universita' Degli Studi Gabriele d'Annunzio Di Chieti

    Chieti, 66100

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, 56126

  • Azienda Ospedaliero Universitaria Policlinico Umberto I

    Roma, 00185

Other trials in Italy

Mexico4 sites

  • Human Science Research Trials

    Mexico City, 14050

  • Grupo Medico Camino SC

    Mexico City, 3310

  • Axis Heilsa S. de R.L. de C.V.

    Nuevo León, Monterrey, 64040

  • Neurociencias Estudios Clínicos SC

    Sinaloa

Other trials in Mexico

Canada3 sites

  • Center for Neurologic Research

    Lethbridge, Alberta, T1J 0N9

  • London Health Sciences Center

    London, Ontario, N6A 5A5

  • Le Centre Hospitalier de l'Universite' de Montreal (CHUM)

    Montreal, H2X 0C1

Other trials in Canada

Croatia3 sites

  • Altavita Centar j.d.o.o.

    Zagreb, 10000

  • Poliklinika Bonifarm

    Zagreb, 10000

  • University Hospital Centre Zagreb

    Zagreb, 10000

Other trials in Croatia

Israel3 sites

  • Hadassah Medical Center (HMC)

    Jerusalem, 9112001

  • Kaplan Medical Center (KMC)

    Rehovot, 76100

  • The Tel Aviv Sourasky Medical Center

    Tel Aviv, 6423906

Other trials in Israel

Austria2 sites

  • University Hospital Innsbruck

    Innsbruck, 6020

  • Universitatsklinik fur Neurologie, Medizinische Universitat Wien

    Vienna, 1090

Other trials in Austria

Belgium2 sites

  • Cliniques Universitaires Saint-Luc (UCL)

    Brussels, 1200

  • Universitair Ziekenhuis Gent

    Ghent, 9000

Other trials in Belgium

Bulgaria2 sites

  • Hospital for active treatmnt Puls AD Neurology Dpt

    Blagoevgrad, 2700

  • MHATNP St. Naum

    Sofia, 1113

Other trials in Bulgaria

Chile2 sites

  • Centro de investigación Clinica UC

    Santiago, 8330073

  • Hospital Clinico Viña del Mar

    Viña del Mar, 2520612

Other trials in Chile

Czechia2 sites

  • Motol University Hospital

    Prague, 150 06

  • Forbeli s.r.o.

    Prague, 160 00

Other trials in Czechia

Georgia2 sites

  • American Hospital Network LLC

    Tbilisi, 0102

  • Institute of Neurology and Neuropsychology

    Tbilisi, 0186

Other trials in Georgia

New Zealand2 sites

  • University of Auckland

    Auckland, 1023

  • Waikato Hospital

    Hamilton, 3204

Other trials in New Zealand

Finland1 site

  • Kuopio University Hospital

    Kuopio, 70 210

Other trials in Finland

Hungary1 site

  • Semmelweis Egyetem, Idegsebeszeti es Neurointervencios Klinika

    Budapest, 1145

Other trials in Hungary

Ireland1 site

  • Beaumont Hospital

    Dublin, NO9 V2NO

Other trials in Ireland

Netherlands1 site

  • Kempenhaeghe

    Heeze

Other trials in Netherlands

About this study

Official title: 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.

Read the 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.

Being tested
XEN1101
Keywords
Epilepsy, Seizures
Medical subject headings
Epilepsies, Partial, Seizures, Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • XEN1101Drug

    Also called Azetukalner

    XEN1101 capsules

Study groups in NCT05718817
Study groupRoleWhat they receive
XEN1101 15 or 25 mg/dayExperimentalXEN1101 15 or 25 mg/day
Receives: Drug: XEN1101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The adverse events

    To assess the safety and tolerability of XEN1101

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

Secondary outcomes (5)

  1. 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.

    Measured: From baseline through the active extension treatment (Week 312).

  2. Proportion of responders

    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.

    Measured: From baseline through the active extension treatment (Week 312).

  3. Change in Clinical Global Impression of Severity (CGI-S)

    Improvement in Clinical Global Impression of Severity (CGI-S) scores over time.

    Measured: From baseline through the active extension treatment (Week 312).

  4. Change in Patient Global Impression of Severity (PGI-S)

    Improvement in Patient Global Impression of Severity (PGI-S) scores over time.

    Measured: From baseline through the active extension treatment (Week 312).

  5. Change in Quality of Life in Epilepsy Inventory (QOLIE-31)

    Change in the 31-Item Quality of Life in Epilepsy Inventory (QOLIE-31) over time.

    Measured: From baseline through the active extension treatment (Week 312).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2023
  2. Study start25 Apr 2023
  3. Primary completionApr 2033 (estimated)
  4. Study completionJun 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
880 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05718817
Sponsor's protocol ID
XPF-010-304
Other IDs
2022-502282-24-00
Acronym
X-TOLE4
Status last verified
Oct 2026
First submitted
13 Jan 2023
Last updated
8 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing XEN1101 in people with Focal Epilepsy and Tonic-Clonic Seizures, run by Xenon Pharmaceuticals Inc. at 152 sites in 25 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 152 sites in United States, Argentina, Spain, Australia, Germany and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The adverse events (time frame: From the start of treatment in the open-label extension (OLE) study through 8 weeks after the last dose.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05718817.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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