A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures

NCT05614063 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: XPF-010-3012022-502000-73-00
• Study Type: interventional
• Target: 380
• Locations: 18 countries
• Sites: 125

Brief Summary

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.

Conditions

Focal Onset Seizures

Keywords

Epilepsy

Outcome Measures

Primary Outcomes (1)

• Median percent change (MPC) in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo.

  From baseline through to the double blind period (week 12)

Secondary Outcomes (4)

• Proportion of subjects experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline through the DBP for XEN1101 versus placebo.

  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.

  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).

  From baseline through to the double blind period (week 12)

• To assess adverse events as criteria for safety and tolerability of XEN1101

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (125)

Strada Patient Care Center

Mobile, Alabama, 36604, United States

Location

Xenoscience

Phoenix, Arizona, 85004, United States

Location

University of Arizona, Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Clinical Trials, Inc

Little Rock, Arkansas, 72205, United States

Location

Brain Science Research Institute

Los Angeles, California, 90025, United States

Location

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

Sacramento, California, 95817, United States

Location

Anschutz Health Sciences

Aurora, Colorado, 80011, United States

Location

Serenity Research

Miami, Florida, 33176, United States

Location

Research Institute of Orlando, LLC

Orlando, Florida, 32806, United States

Location

Panhandle Research & Medical Clinic

Pensacola, Florida, 32503, United States

Location

Medsol Clinical Research Center

Port Charlotte, Florida, 33952, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Encore Medical Research of Weston, LLC

Weston, Florida, 33021, United States

Location

Emory Brain Health Center

Atlanta, Georgia, 30329, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Consultants in Epilepsy and Neurology

Boise, Idaho, 83702, United States

Location

Indiana University, IU Health Partners, Adult Neurology Clinic

Indianapolis, Indiana, 46202, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Bluegrass Epilepsy Research, LLC

Lexington, Kentucky, 40504, United States

Location

University of Kentucky, Dept. of Neurology

Lexington, Kentucky, 40536-0284, United States

Location

MaineHealth Neurology - Scarborough

Scarborough, Maine, 04074, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Medstar Franklin Square Medical Center

Baltimore, Maryland, 21237, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

MedStar Georgetown University Hospital

Clinton, Maryland, 20735, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Cornwell Health

Grand Rapids, Michigan, 49506, United States

Location

Minneapolis Clinic of Neurology

Burnsville, Minnesota, 55337, United States

Location

Saint Louis University Medical School - Neurosciences Clinical Research Unit

St Louis, Missouri, 63104, United States

Location

Washington University, St. Louis

St Louis, Missouri, 63110, United States

Location

Northeast Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

Dent Neurosciences Research Center

Buffalo, New York, 14226, United States

Location

NYU Comprehensive Epilepsy Center (CEC)

New York, New York, 10016, United States

Location

Weill Cornell Medicine/ New York-Presbyterian Hospital

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467-2401, United States

Location

Onsite Clinical Solutions, LLC

Charlotte, North Carolina, 28211, United States

Location

Duke Neurology

Durham, North Carolina, 27713, United States

Location

Meridian Clinical Research, LLC

Raleigh, North Carolina, 27607, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Summa Health

Akron, Ohio, 44304, United States

Location

Providence Brain & Spine Institute

Portland, Oregon, 97225, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140-4105, United States

Location

Austin Epilepsy Care Center (AECC)

Austin, Texas, 78758, United States

Location

ANESC Research

El Paso, Texas, 79912, United States

Location

UT Physicians Epilepsy Clinic

Houston, Texas, 77030, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

Carilion Clinic - Neurology

Roanoke, Virginia, 24013, United States

Location

Sentara Neurology Specialists

Virginia Beach, Virginia, 23456, United States

Location

University of Washington Main Hospital

Seattle, Washington, 98104, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

INECO and Favoloro Fundation

Buenos Aires, 1060, Argentina

Location

Hospital General de Agudos J.M. Ramos Mejia

Buenos Aires, 1221, Argentina

Location

Hospital De Alta Complejidad en Red el Cruce Nestor Kirchner - SAMIC

Buenos Aires, B1888AAE, Argentina

Location

STAT Research S.A.

Buenos Aires, C1023AAB, Argentina

Location

Hospital Italiano

Buenos Aires, C1199ABB, Argentina

Location

CENyR

Caba, C1424, Argentina

Location

Hospital Córdoba

Córdoba, CP 5000, Argentina

Location

Sanatorio del Sur S.A.

San Miguel de Tucumán, 4000, Argentina

Location

St Vincent's Hospital Melbourne

Fitzroy, Melbourne, 3065, Australia

Location

Royal Prince Alfred Hospital (RAPH)

Camperdown, New South Wales, 2050, Australia

Location

Prince of Wales Hospital

Sydney, New South Wales, 2031, Australia

Location

Southern Neurology

Sydney, New South Wales, 2217, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

The University of Queensland (UQ) - Mater Research Institute (MRI)

Brisbane, Queensland, 4101, Australia

Location

Austin Health Pharmacy Clinical Trials

Heidelberg, Victoria, 3079, Australia

Location

The Alfred Hospital (Alfred Health)

Melbourne, Victoria, 3004, Australia

Location

The Royal Melbourne Hospital

Melbourne, 3052, Australia

Location

MHAT Puls AD

Blagoevgrad, 2700, Bulgaria

Location

Center For Neurologic Research

Lethbridge, Alberta, T1J 0N9, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

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

Montreal, Quebec, H2X3E4, Canada

Location

Centro de investigación Clinica UC

Santiago, 833073, Chile

Location

Hospital Clínico Vina del Mar

Viña del Mar, 2520612, Chile

Location

FORBELI s.r.o., Neurologicka ambulance

Prague, 160-00, Czechia

Location

American Hospital Network LLC

Tbilisi, 0121, Georgia

Location

Institute of Neurology and Neuropsychology

Tbilisi, 0186, Georgia

Location

Epilepsy Center Bethel

Bielefeld, 33617, Germany

Location

Universitatsklinikum Bonn

Bonn, Germany

Location

Epilepsiezentrum Frankfurt Rhein-Main

Frankfurt, 60528, Germany

Location

University Medical Center Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Philipps-Universität Marburg

Marburg, 35043, Germany

Location

LMU Munich, Department of Neurology

Munich, 81277, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitatsklinik fur neurologie, universitats - und Rehabilitationskliniken Ulm

Ulm, 89081, Germany

Location

Beaumont Hospital

Dublin, D09 YD60, Ireland

Location

Istituto delle Scienze Neurologiche di Bologna

Bologna, 40139, Italy

Location

Università Degli Studi Gabriele d'Annunzio Di Chieti

Pescara, 66100, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56100, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico Umberto I

Rome, 00186, Italy

Location

Pauls Stradina Clinical university hospital

Riga, LV-1002, Latvia

Location

Riga East University Hospital

Riga, LV-1024, Latvia

Location

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

Mexico City, 14050, Mexico

Location

Neurocencias Esudios Clinicos SC

Sinaloa, 80020, Mexico

Location

University of Auckland

Auckland, 1023, New Zealand

Location

Waikato Hospital

Hamilton, 3204, New Zealand

Location

Centrum Medyczne Neuromed

Bydgoszcz, 85-163, Poland

Location

NZOZ Novo-Med

Katowice, 40-650, Poland

Location

Twoja Przychodnia NCM

Nowa Sól, 67-100, Poland

Location

Neurosphera Sp. z o.o.

Warsaw, 02-829, Poland

Location

Unidade Local de Saúde de São João

Porto, 4200-450, Portugal

Location

Hospital Pedro Hispano

Porto, 4464-513, Portugal

Location

Centro Hospitalar de Entre o Douro e Vouga

Santa Maria da Feira, 4520-220, Portugal

Location

Unitat d'Assaigs Clínics. Servei de Farmàcia

Barcelona, 08036, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

Hospital Vithas La Milagrosa

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

IIS-Fundacion Jimenez Diaz/Farmacia

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional De Malaga

Málaga, 29010, Spain

Location

Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

Location

Hospital Clínico Universitario Valladolid

Valladolid, 47003, Spain

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B152GW, United Kingdom

Location

University Hospital of Wales

Cardiff, CF144XW, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

St. George's Hospital NHS Foundation Trust

London, SW17 0QT, United Kingdom

Location

Royal London Hospital for Integrated Medicine

London, WC1N 3HR, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Northern Care Alliance NHS Foundation Trust, Salford Care Organisation

Salford, M6 8HD, United Kingdom

Location

MeSH Terms

Conditions

Seizures; Epilepsy

Interventions

XEN1101

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Study Officials

• Medical Director

  Xenon Pharmaceuticals Inc.

  STUDY DIRECTOR

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: November 6, 2022
• First Posted: November 14, 2022
• Study Start: November 18, 2022
• Primary Completion: January 12, 2026
• Study Completion: February 3, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1); PL (4); CZ (1); ME (2); PT (3); AR (8); DE (8); NZ (2); LA (2); GB (7); CA (3); AU (9); US (56); CL (2); ES (10); IE (1); GE (2); IT (4)