A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures

NCT ID: NCT05667142

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-14

Study Completion Date

2027-06-30

Brief Summary

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This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in primary generalized tonic-clonic seizures (PGTCS).

Detailed Description

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This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in subjects diagnosed with generalized epilepsy and experiencing probable or possible PGTCS (with or without other subtypes of generalized seizures), and taking 1 to 3 anti-seizure medications (ASMs). Eligible subjects will be randomly assigned 1:1 to XEN1101 or placebo: subjects aged ≥ 18 years will receive XEN1101 25 mg or placebo, and subjects aged ≥12 years and \<18 years will receive either XEN1101 15 mg, 25 mg, or placebo. Randomization will be stratified based on region, age group, and background use of CYP3A4-inducer ASMs. Eligible subjects will have up to 9.5 weeks durations to assess the baseline frequency of seizures, followed by a double-blind treatment period (DBP) where subjects will receive 12 weeks of blinded treatment. 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 enroll in a separate open-label-extension (OLE) study for continued treatment with XEN1101. Subjects who do not enroll in the OLE will enter an 8 week post-treatment follow-up period.

Conditions

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Primary Generalized Tonic-Clonic Seizures

Keywords

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Epilepsy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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XEN1101 25 mg/day

XEN1101 25 mg/day

Group Type EXPERIMENTAL

XEN1101

Intervention Type DRUG

XEN1101 capsules

XEN1101 15 mg/day

XEN1101 15 mg/day

Group Type EXPERIMENTAL

XEN1101

Intervention Type DRUG

XEN1101 capsules

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo capsules

Interventions

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XEN1101

XEN1101 capsules

Intervention Type DRUG

Placebo

Placebo capsules

Intervention Type DRUG

Other Intervention Names

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Azetukalner

Eligibility Criteria

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Inclusion Criteria

1. Subject is properly informed of the nature and risks of the study and gives informed consent in writing prior to entering the study (for adult subjects) and for adolescent subjects parent/legal guardian and subject gives informed consent or assent in writing prior to entering the study.
2. Subject is ≥12 years of age with a BMI ≤40 kg/m2 at Visit 1.
3. 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.
4. Subject has probable or possible PGTCS (with or without other subtypes of generalized seizures) for ≥1 year, in the setting of generalized epilepsy according to the International League Against Epilepsy 2017 classification criteria, and subject is approved by The Epilepsy Study Consortium (TESC).
5. Subject is on a stable dose of 1 to 3 allowable current ASMs for at least 1 month prior to screening (Visit 1), during screening/baseline, and throughout the DBP.
6. Subject is able to keep accurate seizure diaries.

Exclusion Criteria

1. Subject has had status epilepticus within the 12 months prior to Visit 1.
2. Subject has history of repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
3. Subject has a history of non-epileptic psychogenic seizures.
4. Subject has a concomitant diagnosis of focal-onset seizures (FOS).
5. Subject has presence or history of a developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
6. Subject has 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.
7. Subject has history of neurosurgery for seizures \<1 year prior to Visit 1, or radiosurgery \<2 years prior to Visit 1.
8. Subject has schizophrenia and other psychotic disorders (eg, schizophreniform disorder, schizoaffective disorder, psychosis not otherwise specified), bipolar disorder, obsessive-compulsive disorder, or another serious mental health disorder. Subject has uncontrolled unipolar major depression where changes in pharmacotherapy are needed or anticipated during the study.
9. Subject has any clinically significant laboratory abnormalities or clinically significant abnormalities on prestudy physical examination, vital signs, or ECG that, in the judgment of the investigator, indicate a medical problem that would preclude study participation, including but not limited to:

a. History or presence of long QT syndrome; QTcF \>450 msec at baseline; family history of sudden death of unknown cause.
10. Any personal circumstance that, in the opinion of the investigator, prevents adherence to the protocol.

The criteria to be eligible for randomization are:

1. During the last 56 days of the baseline period that preceded the randomization visit (Visit 2), subject must have had a sufficient documented seizure frequency of PGTCS, including ≥1 PGTCS during each of the first and second 4-week periods preceding randomization.
2. Seizure diary was completed a minimum of 80% of all days (ie, ≥45 days) during the last 56 days of the baseline period that preceded randomization as evidence of adequate compliance.
3. Subject did not change dose of, stop, or initiate any new ASM(s) during the baseline period and plans on maintaining a stable dose of ASM(s) during the DBP.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Worldwide Clinical Trials

OTHER

Sponsor Role collaborator

Xenon Pharmaceuticals Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Xenon Pharmaceuticals Inc.

Locations

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University of Alabama - Strada Patient Care Center, Neurology

Mobile, Alabama, United States

Site Status RECRUITING

Xenoscience

Phoenix, Arizona, United States

Site Status RECRUITING

University of Arizona - Health Science Center

Tucson, Arizona, United States

Site Status RECRUITING

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status RECRUITING

Brain Science Research Institute

Los Angeles, California, United States

Site Status RECRUITING

University of California, Irvine - Health Neurology Services

Orange, California, United States

Site Status RECRUITING

University California, Davis Clinical & Translation Science Center Clinical Research (CCRC)

Sacramento, California, United States

Site Status RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Site Status RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status RECRUITING

Serenity Research Center, LLC

Miami, Florida, United States

Site Status RECRUITING

Research Institute of Orlando, LLC

Orlando, Florida, United States

Site Status TERMINATED

Panhandle Research and Medical Clinic

Pensacola, Florida, United States

Site Status RECRUITING

Medsol Clinical Research Center Harbor Professional Centre

Port Charlotte, Florida, United States

Site Status RECRUITING

University of South Florida

Tampa, Florida, United States

Site Status RECRUITING

Encore Medical Research of Weston, LLC

Weston, Florida, United States

Site Status RECRUITING

Emory Brain Health Center

Atlanta, Georgia, United States

Site Status RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status RECRUITING

Georgia Neurology & Sleep Medicine Associates

Suwanee, Georgia, United States

Site Status WITHDRAWN

Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center

Honolulu, Hawaii, United States

Site Status RECRUITING

Consultants in Epilepsy and Neurology, PLLC

Boise, Idaho, United States

Site Status RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status RECRUITING

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status RECRUITING

Bluegrass Epilepsy Research, LLC

Lexington, Kentucky, United States

Site Status RECRUITING

University of Kentucky Albert B. Chandler Hospital (UK Healthcare)

Lexington, Kentucky, United States

Site Status RECRUITING

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status RECRUITING

MedStar Franklin Square Medical Center

Baltimore, Maryland, United States

Site Status RECRUITING

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Site Status RECRUITING

Medstar Georgetown University Hospital

Clinton, Maryland, United States

Site Status RECRUITING

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, United States

Site Status RECRUITING

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status RECRUITING

University of Michigan Hospitals

Ann Arbor, Michigan, United States

Site Status RECRUITING

Wayne State University

Detroit, Michigan, United States

Site Status RECRUITING

Michigan State University Department of Neurology

East Lansing, Michigan, United States

Site Status RECRUITING

Spectrum Health

Grand Rapids, Michigan, United States

Site Status RECRUITING

Saint Louis University Medical School

St Louis, Missouri, United States

Site Status RECRUITING

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States

Site Status RECRUITING

Dent Neurosciences Research Facility

Amherst, New York, United States

Site Status TERMINATED

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status RECRUITING

Five Towns Neurology

Woodmere, New York, United States

Site Status WITHDRAWN

Atrium Health

Charlotte, North Carolina, United States

Site Status RECRUITING

Onsite Clinical Solutions, LLC

Charlotte, North Carolina, United States

Site Status RECRUITING

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Summa Health Clinical Research Center

Akron, Ohio, United States

Site Status RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status RECRUITING

The Ohio State University

Columbus, Ohio, United States

Site Status RECRUITING

OhioHealth Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

UPMC Comprehensive Epilepsy Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Site Status WITHDRAWN

ANESC Research

El Paso, Texas, United States

Site Status RECRUITING

UTHealth Science Center at Houston

Houston, Texas, United States

Site Status RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

University of Utah Clinical Neurosciences Center

Salt Lake City, Utah, United States

Site Status RECRUITING

Sentara Neurology Specialists

Virginia Beach, Virginia, United States

Site Status RECRUITING

University of Washington, Regional Epilepsy Center at Harborview Medical Center

Seattle, Washington, United States

Site Status RECRUITING

Advocate Aurora Research institute, St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Hospital General de Agudos J.M. Ramos Mejia

Buenos Aires, , Argentina

Site Status RECRUITING

STAT Research S.A.

Buenos Aires, , Argentina

Site Status RECRUITING

Hospital Italiano

Buenos Aires, , Argentina

Site Status RECRUITING

Sanatorio del Sur S.A

San Miguel de Tucumán, , Argentina

Site Status RECRUITING

Southern Neurology

Kogarah, New South Wales, Australia

Site Status RECRUITING

Mater Misericordiae Ltd

South Brisbane, Queensland, Australia

Site Status RECRUITING

The Alfred Hospital

Melbourne, VC, Australia

Site Status RECRUITING

Austin Health Pharmacy Clinical Trials

Heidelberg, Victoria, Australia

Site Status RECRUITING

St Vincent's Hospital Melbourne, Clinical Neurosciences

Melbourne, Victoria, Australia

Site Status RECRUITING

The Royal Melbourne Hospital

Parkville, , Australia

Site Status RECRUITING

University Hospital Innsbruck

Innsbruck, , Austria

Site Status RECRUITING

Universitaetsklinik fuer Kinder

Linz, , Austria

Site Status RECRUITING

Universitätsklinik für Neurologie

Salzburg, , Austria

Site Status RECRUITING

Universitätsklinik für Neurologie, Medizinische Universität Wien

Vienna, , Austria

Site Status RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status RECRUITING

Multiprofile hospital for active treatment Puls AD

Blagoevgrad, , Bulgaria

Site Status RECRUITING

MHATNP 'Sveti Naum' EAD

Sofia, , Bulgaria

Site Status RECRUITING

First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel

Sofia, , Bulgaria

Site Status WITHDRAWN

Center for Neurologic Research

Lethbridge, Alberta, Canada

Site Status RECRUITING

Children and Women's Health Centre of BC (BC Children's Hospital)

Vancouver, British Columbia, Canada

Site Status RECRUITING

London Health Sciences Center

London, Ontario, Canada

Site Status RECRUITING

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

Montreal, Quebec, Canada

Site Status RECRUITING

Centro de investigación Clinica UC-CICUC

Santiago, , Chile

Site Status RECRUITING

Clinical Hospital Center Osijek

Osijek, , Croatia

Site Status WITHDRAWN

Clinical Hospital Center Rijeka

Rijeka, , Croatia

Site Status WITHDRAWN

University Hospital Center Zagreb

Zagreb, , Croatia

Site Status WITHDRAWN

Fakultni nemocnice v Motole Neurologicka klinika 2. LF UK a FN Motol

Prague, , Czechia

Site Status WITHDRAWN

CHU de Lille, Hôpital Roger Salengro - Neurophysiologie clinique

Lille, , France

Site Status RECRUITING

Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon

Lyon, , France

Site Status RECRUITING

Hôpital Fondation A. de Rothschild

Paris, , France

Site Status RECRUITING

CHU de Rennes - Hôpital Pontchaillou

Rennes, , France

Site Status RECRUITING

CHU de Strasbourg - Hôpital de Hautepierre

Strasbourg, , France

Site Status RECRUITING

Universitätsklinikum Aachen

Aachen, , Germany

Site Status RECRUITING

Vivantes Humboldt Klinikum

Berlin, , Germany

Site Status WITHDRAWN

Bethel Epilepsy Centre

Bielefeld, , Germany

Site Status RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Site Status RECRUITING

Epilepsiezentrum im Neuozentrum

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Philipps-Universität Marburg

Marburg, , Germany

Site Status RECRUITING

Klinikum der Universität München

München, , Germany

Site Status RECRUITING

Epilepsiezentrum Kleinwachau gemeinnützige GmbH

Radeberg, , Germany

Site Status WITHDRAWN

Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status RECRUITING

Universitätsklinikum Ulm

Ulm, , Germany

Site Status RECRUITING

Hadassah University Medical Center

Jerusalem, , Israel

Site Status RECRUITING

The Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status RECRUITING

Kaplan Medical Center

Rehovot, , Israel

Site Status RECRUITING

The Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status RECRUITING

Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona

Ancona, , Italy

Site Status RECRUITING

Università Degli Studi Gabriele d'Annunzio Di Chieti

Chieti, , Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Site Status RECRUITING

Ospedalo Pediatrico Bambino Gesu

Roma, , Italy

Site Status RECRUITING

Policlinico Umberto I

Roma, , Italy

Site Status RECRUITING

Grupo Medico Camino SC

Mexico City, , Mexico

Site Status RECRUITING

Human Science Research Trials S. de R.L. de C.V.

Mexico City, , Mexico

Site Status RECRUITING

Neurociencias Estudios Clínicos S.C

Sinaloa, , Mexico

Site Status RECRUITING

Kempenhaeghe

Heeze, , Netherlands

Site Status RECRUITING

Centrum Medyczne Neuromed

Bydgoszcz, , Poland

Site Status RECRUITING

COPERNICUS Podmiot Leczniczy Sp. z o.o.

Gdansk, , Poland

Site Status RECRUITING

Novo-Med Zielinski I Wspolnicy Sp. J.

Katowice, , Poland

Site Status RECRUITING

NZOZ Neuromed M. i M.

Lublin, , Poland

Site Status WITHDRAWN

Twoja Przychodnia Nowosolskie Centrum Medyczne

Nowa Sól, , Poland

Site Status RECRUITING

Centro Hospitalar Universitário de Coimbra (CHUC)

Coimbra, , Portugal

Site Status RECRUITING

Hospital da Senhora da Oliveira

Guimarães, , Portugal

Site Status RECRUITING

Centro Hospitalar Lisboa Ocidental, Hospital Egas Moniz

Lisbon, , Portugal

Site Status RECRUITING

Centre Hospitalar Universitario de Lisboa Norte (CHULN)

Lisbon, , Portugal

Site Status RECRUITING

Unidade Local de Saúde de Matosinhos

Matosinhos Municipality, , Portugal

Site Status RECRUITING

Centro Hospitalar Universitário de Santo António

Porto, , Portugal

Site Status RECRUITING

Centro Hospitalar de Entre o Douro e Vouga

Santa Maria da Feira, , Portugal

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Vithas Madrid La Milagrosa

Madrid, , Spain

Site Status RECRUITING

Hospital Regional Universitario de Málaga

Málaga, , Spain

Site Status RECRUITING

Hospital Clinico Universitario de Valladolid

Valladolid, , Spain

Site Status RECRUITING

Hospital Clinico Viña del Mar

Valparaíso, , Spain

Site Status RECRUITING

University Hospital of Wales

Cardiff, Wales, United Kingdom

Site Status RECRUITING

Mid Yorkshire Hospitals NHS Trust

Wakefield, West Yorkshire, United Kingdom

Site Status RECRUITING

St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status RECRUITING

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

Salford, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Australia Austria Belgium Bulgaria Canada Chile Croatia Czechia France Germany Israel Italy Mexico Netherlands Poland Portugal Spain United Kingdom

Central Contacts

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Xenon Medical Affairs

Role: CONTACT

Phone: 1-604-484-3300

Email: [email protected]

Other Identifiers

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2022-502286-16-00

Identifier Type: CTIS

Identifier Source: secondary_id

XPF-010-303

Identifier Type: -

Identifier Source: org_study_id