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

NCT05667142 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: XPF-010-3032022-502286-16-00
• Study Type: interventional
• Target: 160
• Locations: 19 countries
• Sites: 132

Brief Summary

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).

Conditions

Primary Generalized Tonic-Clonic Seizures

Keywords

Epilepsy

Outcome Measures

Primary Outcomes (1)

• Median percent change (MPC) in monthly (28 days) PGTCS frequency

  Median percent change (MPC) in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo.

  Baseline through DBP (Week 12)

Secondary Outcomes (2)

• Proportion of subjects

  Baseline through DBP (Week 12)

• Proportion of subjects

  Baseline through Week 12

Other Outcomes (1)

• Incidence of adverse events

  From Screening Through to 56 Days Post-Final Dose

Study Arms (3)

XEN1101 25 mg/day

EXPERIMENTAL

XEN1101 25 mg/day

Drug: XEN1101

XEN1101 15 mg/day

EXPERIMENTAL

XEN1101 15 mg/day

Drug: XEN1101

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

XEN1101 DRUG

XEN1101 capsules

Also known as: Azetukalner

XEN1101 15 mg/day; XEN1101 25 mg/day

Placebo DRUG

Placebo capsules

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subject is ≥12 years of age with a BMI ≤40 kg/m2 at Visit 1.
• 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.
• 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).
• 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.
• Subject is able to keep accurate seizure diaries.

You may not qualify if:

• Subject has had status epilepticus within the 12 months prior to Visit 1.
• Subject has history of repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
• Subject has a history of non-epileptic psychogenic seizures.
• Subject has a concomitant diagnosis of focal-onset seizures (FOS).
• Subject has presence or history of a developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
• 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.
• Subject has history of neurosurgery for seizures \<1 year prior to Visit 1, or radiosurgery \<2 years prior to Visit 1.
• 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.
• 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.
• Any personal circumstance that, in the opinion of the investigator, prevents adherence to the protocol.
• The criteria to be eligible for randomization are:
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Xenon Pharmaceuticals Inc.: lead
• Worldwide Clinical Trials: collaborator

Study Sites (138)

University of Alabama - Strada Patient Care Center, Neurology

Mobile, Alabama, 36604, United States

RECRUITING

Xenoscience

Phoenix, Arizona, 85004, United States

RECRUITING

University of Arizona - Health Science Center

Tucson, Arizona, 85724, United States

RECRUITING

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

RECRUITING

Brain Science Research Institute

Los Angeles, California, 90025, United States

RECRUITING

University of California, Irvine - Health Neurology Services

Orange, California, 92868, United States

RECRUITING

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

Sacramento, California, 95817, United States

WITHDRAWN

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Serenity Research Center, LLC

Miami, Florida, 33176, United States

RECRUITING

Research Institute of Orlando, LLC

Orlando, Florida, 32806, United States

TERMINATED

Panhandle Research and Medical Clinic

Pensacola, Florida, 32503, United States

RECRUITING

Medsol Clinical Research Center Harbor Professional Centre

Port Charlotte, Florida, 33952, United States

RECRUITING

University of South Florida

Tampa, Florida, 33606, United States

RECRUITING

Encore Medical Research of Weston, LLC

Weston, Florida, 33331, United States

RECRUITING

Emory Brain Health Center

Atlanta, Georgia, 30329, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

RECRUITING

Georgia Neurology & Sleep Medicine Associates

Suwanee, Georgia, 30024, United States

WITHDRAWN

Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center

Honolulu, Hawaii, 96817, United States

RECRUITING

Consultants in Epilepsy and Neurology, PLLC

Boise, Idaho, 83702, United States

RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, 62794, United States

RECRUITING

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

WITHDRAWN

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Bluegrass Epilepsy Research, LLC

Lexington, Kentucky, 40504, United States

RECRUITING

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

Lexington, Kentucky, 40536, United States

RECRUITING

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

RECRUITING

MedStar Franklin Square Medical Center

Baltimore, Maryland, 21237, United States

RECRUITING

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

RECRUITING

Medstar Georgetown University Hospital

Clinton, Maryland, 20735, United States

RECRUITING

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, 02467, United States

RECRUITING

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

RECRUITING

University of Michigan Hospitals

Ann Arbor, Michigan, 48109, United States

RECRUITING

Wayne State University

Detroit, Michigan, 48201, United States

RECRUITING

Michigan State University Department of Neurology

East Lansing, Michigan, 48824, United States

RECRUITING

Spectrum Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

Saint Louis University Medical School

St Louis, Missouri, 14624, United States

RECRUITING

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

RECRUITING

Dent Neurosciences Research Facility

Amherst, New York, 14226, United States

TERMINATED

SUNY Upstate Medical University

Syracuse, New York, 13201, United States

RECRUITING

Five Towns Neurology

Woodmere, New York, 11598, United States

WITHDRAWN

Atrium Health

Charlotte, North Carolina, 28203, United States

RECRUITING

Onsite Clinical Solutions, LLC

Charlotte, North Carolina, 28211, United States

RECRUITING

Duke University Clinical Research

Durham, North Carolina, 27710, United States

RECRUITING

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27104, United States

RECRUITING

Summa Health Clinical Research Center

Akron, Ohio, 44304, United States

RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

OhioHealth Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

UPMC Comprehensive Epilepsy Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

WITHDRAWN

ANESC Research

El Paso, Texas, 79912, United States

RECRUITING

UTHealth Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

University of Utah Clinical Neurosciences Center

Salt Lake City, Utah, 84132, United States

RECRUITING

Sentara Neurology Specialists

Virginia Beach, Virginia, 23456, United States

RECRUITING

University of Washington, Regional Epilepsy Center at Harborview Medical Center

Seattle, Washington, 98104, United States

RECRUITING

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

Milwaukee, Wisconsin, 53215, United States

RECRUITING

Hospital General de Agudos J.M. Ramos Mejia

Buenos Aires, 1221, Argentina

RECRUITING

STAT Research S.A.

Buenos Aires, C1023AAB, Argentina

RECRUITING

Hospital Italiano

Buenos Aires, C1181ACH, Argentina

RECRUITING

Sanatorio del Sur S.A

San Miguel de Tucumán, 4000, Argentina

RECRUITING

Southern Neurology

Kogarah, New South Wales, 2217, Australia

WITHDRAWN

Mater Misericordiae Ltd

South Brisbane, Queensland, 4101, Australia

RECRUITING

The Alfred Hospital

Melbourne, VC, 3004, Australia

RECRUITING

Austin Health Pharmacy Clinical Trials

Heidelberg, Victoria, 3084, Australia

RECRUITING

St Vincent's Hospital Melbourne, Clinical Neurosciences

Melbourne, Victoria, 3065, Australia

RECRUITING

The Royal Melbourne Hospital

Parkville, 3050, Australia

RECRUITING

University Hospital Innsbruck

Innsbruck, 6020, Austria

RECRUITING

Universitaetsklinik fuer Kinder

Linz, 4021, Austria

RECRUITING

Universitätsklinik für Neurologie

Salzburg, 5020, Austria

RECRUITING

Universitätsklinik für Neurologie, Medizinische Universität Wien

Vienna, 1090, Austria

RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

Multiprofile hospital for active treatment Puls AD

Blagoevgrad, 2700, Bulgaria

RECRUITING

MHATNP 'Sveti Naum' EAD

Sofia, 1113, Bulgaria

RECRUITING

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

Sofia, 1142, Bulgaria

WITHDRAWN

Center for Neurologic Research

Lethbridge, Alberta, T1J 0N9, Canada

RECRUITING

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

Vancouver, British Columbia, V6H 3V4, Canada

RECRUITING

London Health Sciences Center

London, Ontario, N6A5A5, Canada

RECRUITING

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

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

Centro de investigación Clinica UC-CICUC

Santiago, Chile

RECRUITING

Clinical Hospital Center Osijek

Osijek, 310 00, Croatia

WITHDRAWN

Clinical Hospital Center Rijeka

Rijeka, 510 00, Croatia

WITHDRAWN

University Hospital Center Zagreb

Zagreb, 100 00, Croatia

WITHDRAWN

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

Prague, 150 06, Czechia

WITHDRAWN

CHU de Lille, Hôpital Roger Salengro - Neurophysiologie clinique

Lille, 59037, France

RECRUITING

Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon

Lyon, 9003, France

RECRUITING

Hôpital Fondation A. de Rothschild

Paris, 75019, France

RECRUITING

CHU de Rennes - Hôpital Pontchaillou

Rennes, 35033, France

RECRUITING

CHU de Strasbourg - Hôpital de Hautepierre

Strasbourg, 67098, France

RECRUITING

Universitätsklinikum Aachen

Aachen, D-52074, Germany

RECRUITING

Vivantes Humboldt Klinikum

Berlin, 13509, Germany

WITHDRAWN

Bethel Epilepsy Centre

Bielefeld, 33617, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, 60528, Germany

RECRUITING

Epilepsiezentrum im Neuozentrum

Freiburg im Breisgau, 79106, Germany

RECRUITING

Philipps-Universität Marburg

Marburg, 35043, Germany

RECRUITING

Klinikum der Universität München

München, 81377, Germany

RECRUITING

Epilepsiezentrum Kleinwachau gemeinnützige GmbH

Radeberg, 01454, Germany

WITHDRAWN

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

Hadassah University Medical Center

Jerusalem, 9112001, Israel

RECRUITING

The Chaim Sheba Medical Center

Ramat Gan, 6265601, Israel

RECRUITING

Kaplan Medical Center

Rehovot, 7661041, Israel

RECRUITING

The Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

RECRUITING

Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona

Ancona, 60126, Italy

WITHDRAWN

Università Degli Studi Gabriele d'Annunzio Di Chieti

Chieti, 66100, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

RECRUITING

Ospedalo Pediatrico Bambino Gesu

Roma, 00165, Italy

RECRUITING

Policlinico Umberto I

Roma, 185, Italy

RECRUITING

Grupo Medico Camino SC

Mexico City, 03310, Mexico

RECRUITING

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

Mexico City, 14050, Mexico

RECRUITING

Neurociencias Estudios Clínicos S.C

Sinaloa, 80020, Mexico

RECRUITING

Kempenhaeghe

Heeze, 5591BL VE, Netherlands

RECRUITING

Centrum Medyczne Neuromed

Bydgoszcz, 85-163, Poland

RECRUITING

COPERNICUS Podmiot Leczniczy Sp. z o.o.

Gdansk, 80-803, Poland

RECRUITING

Novo-Med Zielinski I Wspolnicy Sp. J.

Katowice, 40-584, Poland

RECRUITING

NZOZ Neuromed M. i M.

Lublin, 20-064, Poland

WITHDRAWN

Twoja Przychodnia Nowosolskie Centrum Medyczne

Nowa Sól, 67-100, Poland

RECRUITING

Centro Hospitalar Universitário de Coimbra (CHUC)

Coimbra, 3000-075, Portugal

RECRUITING

Hospital da Senhora da Oliveira

Guimarães, 4835-044, Portugal

RECRUITING

Centro Hospitalar Lisboa Ocidental, Hospital Egas Moniz

Lisbon, 1349-019, Portugal

RECRUITING

Centre Hospitalar Universitario de Lisboa Norte (CHULN)

Lisbon, 1649-035, Portugal

RECRUITING

Unidade Local de Saúde de Matosinhos

Matosinhos Municipality, 4450-024, Portugal

RECRUITING

Centro Hospitalar Universitário de Santo António

Porto, 4050-342, Portugal

RECRUITING

Centro Hospitalar de Entre o Douro e Vouga

Santa Maria da Feira, 4520-211, Portugal

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 280 41, Spain

RECRUITING

Hospital Universitario Vithas Madrid La Milagrosa

Madrid, 28010, Spain

WITHDRAWN

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

WITHDRAWN

Hospital Clinico Universitario de Valladolid

Valladolid, 47003, Spain

WITHDRAWN

Hospital Clinico Viña del Mar

Valparaíso, 2520612, Spain

RECRUITING

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

RECRUITING

Mid Yorkshire Hospitals NHS Trust

Wakefield, West Yorkshire, WF1 4DG, United Kingdom

RECRUITING

St George's University Hospitals NHS Foundation Trust

London, SW17 0QT, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust

London, WC1N 3BG, United Kingdom

RECRUITING

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

RECRUITING

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

Salford, M6 8HD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Epilepsy

Interventions

XEN1101

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Medical Director

  Xenon Pharmaceuticals Inc.

  STUDY DIRECTOR

Central Study Contacts

Xenon Medical Affairs

CONTACT

1-604-484-3300; XenonCares@xenon-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: December 28, 2022
• Study Start: February 14, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

PT (7); IL (4); ME (3); DE (10); FR (5); NL (1); CL (1); ES (5); CA (4); IT (5); GB (6); US (59); AU (4); CZ (1); BE (2); CR (3); BU (3); PL (5); AR (4)