Focal Onset SeizuresPhase 3NCT05716100
A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3)
A Phase 3 study testing XEN1101 in people with Focal Onset Seizures, run by Xenon Pharmaceuticals Inc. at 98 sites in 21 countries.
Trial summary
The X-TOLE3 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Focal Onset Seizures
- What is being tested?
- XEN1101
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 360 participants
- Where
- 98 sitesin 21 countries
- Study dates
- 9 May 2023to Mar 2028
- Phase
- Phase 3
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
98 sites in 21 countries. Contact the study team or a site near you to ask about taking part.
98 sites in 21 countries
United States19 sites, 15 recruiting
- Recruiting
Austin Epilepsy Care Center
Austin, Texas, 78758
- Recruiting
Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland, 20817
- Recruiting
Consultants in Epilepsy and Neurology, PLLC
Boise, Idaho, 83702
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Recruiting
OhioHealth
Columbus, Ohio, 43214
- Recruiting
9D University Health Center
Detroit, Michigan, 48201
- Withdrawn
Rancho Research Institute
Downey, California, 90242
- Recruiting
Duke University Clinic
Durham, North Carolina, 27705
- Recruiting
Panhandle Research and Medical Clinic
Gulf Breeze, Florida, 32651
- Recruiting
Northeast Regional Epilepsy Group
Hackensack, New Jersey, 07601
- Recruiting
Mayo Clinic Florida
Jacksonville, Florida, 32224
- Withdrawn
Clinical Trials, Inc.
Little Rock, Arkansas, 72205
- Recruiting
University of California Los Angeles (UCLA)
Los Angeles, California, 90095
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Recruiting
University of California Irvine Health
Orange, California, 92868
- Recruiting
Providence Neurological Specialities
Portland, Oregon, 97225
- Active, not recruiting
University of Utah Clinical Neurosciences Center
Salt Lake City, Utah, 84132
- Recruiting
Southern Illinois University School of Medicine
Springfield, Illinois, 62794
- Withdrawn
Five Towns Neuroscience Research
Woodmere, New York, 11598
Argentina12 sites
- Active, not recruiting
Hospital Ramos Mejia
Buenos Aires, 1221
- Active, not recruiting
Hospital De Alta Complejidad en Red el Cruce
Buenos Aires, 1888
- Active, not recruiting
Policlinico Lomas
Buenos Aires, B1832BQD
- Active, not recruiting
Instituto de Neurologia Cognitiva (INECO)
Buenos Aires, C1060AAF
- Active, not recruiting
Hospital Italiano
Buenos Aires, C1199ABB
- Active, not recruiting
Hospital Britanico de Buenos Aires
Buenos Aires, C1280AEB
- Active, not recruiting
STAT Resarch S.A.
Buenos Aires
- Active, not recruiting
CENyR Centro de Especialidades Neurologicas y Rehabilitacion
C.a.b.a., C1424
- Active, not recruiting
FLENI
C.a.b.a., C1428DGG
- Active, not recruiting
Hospital Córdoba
Córdoba, X5000
- Active, not recruiting
Hospital Central Ramon Carrilo
San Luis, 5701
- Active, not recruiting
Sanatori del Sur S.A.
San Miguel de Tucumán
Portugal8 sites, 7 recruiting
- Recruiting
Centro Hospitalar Universitário de Coimbra - CHUC
Coimbra
- Recruiting
Hospital da Senhora da Oliveira
Guimarães, 4835-044
- Recruiting
Centro Hospitalar de Lisboa Norte
Lisbon, 1649-035
- Recruiting
Centro Hospitalar Lisboa Ocidental
Lisbon
- Recruiting
Centro Hospitalar Universitário de Santo António
Porto, 4099-001
- Recruiting
Hospital Pedro Hispano
Porto, 4464-513
- Recruiting
Centro Hospitalar de Entre o Douro e Vouga
Santa Maria da Feira, 520-211
- Withdrawn
ULS de Trás-os-Montes e Alto Douro
Vila Real, 5000-508
Australia6 sites
- Active, not recruiting
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
- Active, not recruiting
Alfred Hospital
Melbourne, Victoria, 30004
- Active, not recruiting
Austin Health
Melbourne, Victoria, 3084
- Active, not recruiting
Royal Melbourne Hospital
Melbourne, 3050
- Active, not recruiting
Prince of Wales Hospital
Randwick, New South Wales, 2031
- Active, not recruiting
Westmead Hospital
Westmead, New South Wales, 2145
France6 sites, 6 recruiting
- Recruiting
Hopital Neurologique Pierre Wertheimer
Bron, 69500
- Recruiting
Centre Hospitalier Universitaire de Lille (CHU de Lille)
Lille, 59037
- Recruiting
Hôpital de la Pitié Salpêtrière
Paris, 75013
- Recruiting
Hôpital Fondation A. de Rothschild
Paris, 75019
- Recruiting
Chu de Rennes Hôpital Pontchaillou
Rennes, 35033
- Recruiting
Hôpital de Hautepierre
Strasbourg, 67098
Croatia5 sites, 3 recruiting
- Withdrawn
University Hospital Center Osijek
Osijek, 31000
- Withdrawn
Clinical Hospital Center Rijeka, Klinika za Neurologiju
Rijeka, 51000
- Recruiting
Poliklinika Bonifarm
Zagreb, 10000
- Recruiting
University Hospital Center Zagreb
Zagreb, 10000
- Recruiting
Poliklinika LF MEDICAL
Zagreb, 1000
Poland5 sites, 4 recruiting
- Recruiting
COPERNICUS Podmiot Leczniczy
Gdansk
- Withdrawn
NZOZ Neuromed M. i M. Nastaj Sp. P.
Lublin, 20-064
- Recruiting
Twoja Przychodnia Nowosolskie Centrum Medyczne
Nowa Sól, 67-100
- Recruiting
MTZ Clinical Research Powered by Pratia
Warsaw, 02-172
- Recruiting
Neurosphera Sp. z o.o.
Warsaw, 02-829
Chile4 sites
- Withdrawn
Clinica Universidad de Los Andes
Santiago, 7620157
- Active, not recruiting
Centro de Investigacion Clinica UC
Santiago, 833073
- Withdrawn
CINSAN
Santiago, 8431657
- Active, not recruiting
Hospital Clínico Viña del Mar
Viña del Mar
Israel4 sites, 4 recruiting
- Recruiting
Hadassah Medical Center
Jerusalem, 9112001
- Recruiting
The Chaim Sheba Medical Center
Ramat Gan, 6265601
- Recruiting
Kaplan Medical Center
Rehovot, 76100
- Recruiting
The Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
Mexico4 sites
- Active, not recruiting
Grupo Medico Camino
Benito Juárez
- Active, not recruiting
Human Science Research Trials
Mexico City, 14050
- Active, not recruiting
Axis Heilsa S. de R.L. de C.V. Althian
Monterrey
- Active, not recruiting
Neurocencias Esudios Clinicos S.C.
Sinaloa, 80020
Spain4 sites, 4 recruiting
- Recruiting
Hospital Universitario Cruces
Barakaldo, 48903
- Recruiting
Hospital Unversitario Ramon y Cajal
Madrid, 28034
- Recruiting
Hospital Clínico San Carlos
Madrid, 28040
- Recruiting
Hospital universitario Fundación Jiménez Díaz
Madrid, 28040
Austria3 sites, 3 recruiting
- Recruiting
University Hospital Innsbruck
Innsbruck
- Recruiting
Universitätsklinik für Neurologie
Salzburg, 5020
- Recruiting
Medical University of Vienna
Vienna, 1090
Czechia3 sites, 2 recruiting
- Withdrawn
EUC Hradec Kralove Clinic
Hradec Králové
- Recruiting
Nemocnicni lekarna FN Motol / Motol University Hospital
Prague, 150 06
- Recruiting
Forbeli s.r.o.
Prague
Germany3 sites, 3 recruiting
- Recruiting
Universitätsklinikum Aachen
Aachen, D-52074
- Recruiting
Krankenhaus Mara gGmbH
Bielefeld, 33617
- Recruiting
University Hospital Frankfurt, ZNN - Epilepsy Center Frankfurt Rhine-Main
Frankfurt, 60528
Japan3 sites, 3 recruiting
- Recruiting
Seirei Mikatahara General Hospital
Hamamatsu, Shizuoka, 433-8558
- Recruiting
Itami City Hospital
Itami, Hyōgo, 664-8540
- Recruiting
Tanaka Neurosurgery & Headache Clinic
Kagoshima, 890-0052
Belgium2 sites, 2 recruiting
- Recruiting
Cliniques Universitaires Saint-Luc (UCL)
Brussels, 1200
- Recruiting
Universitair Ziekenhuis Gent
Ghent, 9000
Bulgaria2 sites
- Active, not recruiting
MHATNPsy Sveti Naum EAD
Sofia, 1113
- Withdrawn
Medical center OPHTHA-NEURO
Sofia, 1172
Italy2 sites
- Withdrawn
Ospedali Riuniti di Ancona
Ancona, 60126
- Withdrawn
Università degli studi di Bari Aldo Moro
Bari, 70124
Finland1 site, 1 recruiting
- Recruiting
Kuopio University Hospital
Kuopio, 70210
Hungary1 site
- Active, not recruiting
Semmelweis Egyetem, Idegsebészeti és Neurointervenciós Klinika
Budapest, 1145
About this study
Official title: 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-TOLE3 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.
Read the 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.
- Conditions
- Focal Onset Seizures
- Being tested
- XEN1101, Placebo
- Keywords
- Epilepsy
- Medical subject headings
- 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
PlaceboDrug
Placebo Capsules
| Study group | Role | What they receive |
|---|---|---|
| XEN1101 25 mg/day | Experimental | XEN1101 25 mg/day Receives: Drug: XEN1101 |
| XEN1101 15 mg/day | Experimental | XEN1101 15 mg/day Receives: Drug: XEN1101 |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median percent change (MPC) in focal seizure frequency from baseline to DBP for XEN1101 versus placebo.
Measured: From baseline through to the double blind period (week 12).
Secondary outcomes (4)
Proportion of subjects experiencing ≥50% reduction in focal seizure frequency from baseline through the DBP for XEN1101 versus placebo.
Measured: 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.
Measured: 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).
Measured: From baseline through to the double blind period (week 12).
To assess adverse events as criteria for safety and tolerability of XEN1101.
Measured: From screening through to 56 days post-final dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2023
- Study start9 May 2023
- Primary completionJan 2028 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Focal Onset SeizuresStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 360 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xenon Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Worldwide Clinical Trials
- Responsible party
- Sponsor
- Investigators
- Xenon Medical Director, Study director, Xenon Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05716100
- Sponsor's protocol ID
- XPF-010-302
- Other IDs
- 2022-502281-25-00
- Status last verified
- Oct 2026
- First submitted
- 26 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