Primary Generalized Tonic-Clonic SeizuresPhase 3X-ACKTNCT05667142
A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures
A Phase 3 study testing XEN1101 in people with Primary Generalized Tonic-Clonic Seizures, run by Xenon Pharmaceuticals Inc. at 138 sites in 20 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Primary Generalized Tonic-Clonic 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
- 160 participants
- Where
- 138 sitesin 20 countries
- Study dates
- 14 Feb 2023to Jun 2027
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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 3 months prior to the planned randomization (Visit 2), during screening/baseline, and throughout the DBP.
- Subject is able to keep accurate seizure diaries.
Who cannot join
- 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 within 10 years prior to Visit 1.
- 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.
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- 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, 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:
- 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 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. Retrospective seizure data documented up to 4 weeks prior to Visit 1 may be used in combination with a minimum of 4 weeks of prospective seizure data recorded in the study eDiary.
- Study eDiary was completed a minimum of 80% of all applicable days during the last 28-56 days of the baseline period that preceded randomization as evidence of adequate compliance (eg, >45 of 56 days, if no retrospective data prior to Visit 1 are used).
- Subject did not change dose of, stop, or initiate any new ASM(s) during the 3 months that preceded randomization and plans on maintaining a stable dose of ASM(s) during the DBP.
Trial locations and contacts
138 sites in 20 countries. Contact the study team or a site near you to ask about taking part.
138 sites in 20 countries
United States59 sites, 45 recruiting
- Recruiting
Summa Health Clinical Research Center
Akron, Ohio, 44304
- Terminated
Dent Neurosciences Research Facility
Amherst, New York, 14226
- Recruiting
University of Michigan Hospitals
Ann Arbor, Michigan, 48109
- Recruiting
Emory Brain Health Center
Atlanta, Georgia, 30329
- Recruiting
Children's Healthcare of Atlanta
Atlanta, Georgia, 30342
- Withdrawn
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
- Recruiting
University of Maryland Medical Center
Baltimore, Maryland, 21201
- Recruiting
MedStar Franklin Square Medical Center
Baltimore, Maryland, 21237
- Recruiting
Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland, 20817
- Recruiting
Consultants in Epilepsy and Neurology, PLLC
Boise, Idaho, 83702
- Withdrawn
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
- Recruiting
Atrium Health
Charlotte, North Carolina, 28203
- Recruiting
Onsite Clinical Solutions, LLC
Charlotte, North Carolina, 28211
- Recruiting
Brigham and Women's Hospital
Chestnut Hill, Massachusetts, 02467
- Recruiting
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
- Recruiting
Medstar Georgetown University Hospital
Clinton, Maryland, 20735
- Recruiting
The Ohio State University
Columbus, Ohio, 43210
- Recruiting
OhioHealth Riverside Methodist Hospital
Columbus, Ohio, 43214
- Recruiting
Wayne State University
Detroit, Michigan, 48201
- Recruiting
Duke University Clinical Research
Durham, North Carolina, 27710
- Recruiting
Michigan State University Department of Neurology
East Lansing, Michigan, 48824
- Recruiting
ANESC Research
El Paso, Texas, 79912
- Recruiting
Spectrum Health
Grand Rapids, Michigan, 49503
- Recruiting
Northeast Regional Epilepsy Group
Hackensack, New Jersey, 07601
- Withdrawn
Hawaii Pacific Neuroscience, Comprehensive Epilepsy Center
Honolulu, Hawaii, 96817
- Recruiting
UTHealth Science Center at Houston
Houston, Texas, 77030
- Withdrawn
Indiana University School of Medicine
Indianapolis, Indiana, 46202
- Recruiting
Mayo Clinic Florida
Jacksonville, Florida, 32224
- Recruiting
University of Kansas Medical Center
Kansas City, Kansas, 66160
- Recruiting
Bluegrass Epilepsy Research, LLC
Lexington, Kentucky, 40504
- Recruiting
University of Kentucky Albert B. Chandler Hospital (UK Healthcare)
Lexington, Kentucky, 40536
- Recruiting
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
- Recruiting
Brain Science Research Institute
Los Angeles, California, 90025
- Recruiting
Serenity Research Center, LLC
Miami, Florida, 33176
- Recruiting
Advocate Aurora Research institute, St. Luke's Medical Center
Milwaukee, Wisconsin, 53215
- Withdrawn
University of Alabama - Strada Patient Care Center, Neurology
Mobile, Alabama, 36604
- Recruiting
University of California, Irvine - Health Neurology Services
Orange, California, 92868
- Terminated
Research Institute of Orlando, LLC
Orlando, Florida, 32806
- Recruiting
Panhandle Research and Medical Clinic
Pensacola, Florida, 32503
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
- Withdrawn
Temple University Hospital
Philadelphia, Pennsylvania, 19140
- Recruiting
Xenoscience
Phoenix, Arizona, 85004
- Recruiting
UPMC Comprehensive Epilepsy Center
Pittsburgh, Pennsylvania, 15213
- Withdrawn
Medsol Clinical Research Center Harbor Professional Centre
Port Charlotte, Florida, 33952
- Withdrawn
University California, Davis Clinical & Translation Science Center Clinical Research (CCRC)
Sacramento, California, 95817
- Active, not recruiting
University of Utah Clinical Neurosciences Center
Salt Lake City, Utah, 84132
- Recruiting
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
- Recruiting
University of Washington, Regional Epilepsy Center at Harborview Medical Center
Seattle, Washington, 98104
- Recruiting
Southern Illinois University School of Medicine
Springfield, Illinois, 62794
- Recruiting
Saint Louis University Medical School
St Louis, Missouri, 14624
- Withdrawn
Georgia Neurology & Sleep Medicine Associates
Suwanee, Georgia, 30024
- Recruiting
SUNY Upstate Medical University
Syracuse, New York, 13201
- Recruiting
University of South Florida
Tampa, Florida, 33606
- Recruiting
University of Arizona - Health Science Center
Tucson, Arizona, 85724
- Recruiting
Sentara Neurology Specialists
Virginia Beach, Virginia, 23456
- Recruiting
Encore Medical Research of Weston, LLC
Weston, Florida, 33331
- Recruiting
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27104
- Withdrawn
Five Towns Neurology
Woodmere, New York, 11598
- Withdrawn
UMass Memorial Medical Center
Worcester, Massachusetts, 01655
Germany10 sites, 8 recruiting
- Recruiting
Universitätsklinikum Aachen
Aachen, D-52074
- Withdrawn
Vivantes Humboldt Klinikum
Berlin, 13509
- Recruiting
Bethel Epilepsy Centre
Bielefeld, 33617
- Recruiting
Universitätsklinikum Frankfurt
Frankfurt, 60528
- Recruiting
Epilepsiezentrum im Neuozentrum
Freiburg im Breisgau, 79106
- Recruiting
Philipps-Universität Marburg
Marburg, 35043
- Recruiting
Klinikum der Universität München
München, 81377
- Withdrawn
Epilepsiezentrum Kleinwachau gemeinnützige GmbH
Radeberg, 01454
- Recruiting
Universitätsklinikum Tübingen
Tübingen, 72076
- Recruiting
Universitätsklinikum Ulm
Ulm, 89081
Portugal7 sites, 5 recruiting
- Recruiting
Centro Hospitalar Universitário de Coimbra (CHUC)
Coimbra, 3000-075
- Recruiting
Hospital da Senhora da Oliveira
Guimarães, 4835-044
- Recruiting
Centro Hospitalar Lisboa Ocidental, Hospital Egas Moniz
Lisbon, 1349-019
- Recruiting
Centre Hospitalar Universitario de Lisboa Norte (CHULN)
Lisbon, 1649-035
- Recruiting
Unidade Local de Saúde de Matosinhos
Matosinhos Municipality, 4450-024
- Withdrawn
Centro Hospitalar Universitário de Santo António
Porto, 4050-342
- Withdrawn
Centro Hospitalar de Entre o Douro e Vouga
Santa Maria da Feira, 4520-211
Australia6 sites, 4 recruiting
- Recruiting
Austin Health Pharmacy Clinical Trials
Heidelberg, Victoria, 3084
- Withdrawn
Southern Neurology
Kogarah, New South Wales, 2217
- Recruiting
The Alfred Hospital
Melbourne, VC, 3004
- Withdrawn
St Vincent's Hospital Melbourne, Clinical Neurosciences
Melbourne, Victoria, 3065
- Recruiting
The Royal Melbourne Hospital
Parkville, 3050
- Recruiting
Mater Misericordiae Ltd
South Brisbane, Queensland, 4101
United Kingdom6 sites, 6 recruiting
- Recruiting
University Hospital of Wales
Cardiff, Wales, CF14 4XW
- Recruiting
St George's University Hospitals NHS Foundation Trust
London, SW17 0QT
- Recruiting
University College London Hospitals NHS Foundation Trust
London, WC1N 3BG
- Recruiting
John Radcliffe Hospital
Oxford, OX3 9DU
- Recruiting
Salford Royal NHS Foundation Trust - Greater Manchester Neuroscience Centre (GMNC)
Salford, M6 8HD
- Recruiting
Mid Yorkshire Hospitals NHS Trust
Wakefield, West Yorkshire, WF1 4DG
France5 sites, 5 recruiting
- Recruiting
CHU de Lille, Hôpital Roger Salengro - Neurophysiologie clinique
Lille, 59037
- Recruiting
Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
Lyon, 9003
- Recruiting
Hôpital Fondation A. de Rothschild
Paris, 75019
- Recruiting
CHU de Rennes - Hôpital Pontchaillou
Rennes, 35033
- Recruiting
CHU de Strasbourg - Hôpital de Hautepierre
Strasbourg, 67098
Italy5 sites, 3 recruiting
- Withdrawn
Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona
Ancona, 60126
- Recruiting
Università Degli Studi Gabriele d'Annunzio Di Chieti
Chieti, 66100
- Recruiting
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126
- Recruiting
Ospedalo Pediatrico Bambino Gesu
Roma, 00165
- Withdrawn
Policlinico Umberto I
Roma, 185
Poland5 sites, 4 recruiting
- Recruiting
Centrum Medyczne Neuromed
Bydgoszcz, 85-163
- Recruiting
COPERNICUS Podmiot Leczniczy Sp. z o.o.
Gdansk, 80-803
- Recruiting
Novo-Med Zielinski I Wspolnicy Sp. J.
Katowice, 40-584
- Withdrawn
NZOZ Neuromed M. i M.
Lublin, 20-064
- Recruiting
Twoja Przychodnia Nowosolskie Centrum Medyczne
Nowa Sól, 67-100
Spain5 sites
- Withdrawn
Hospital Universitario 12 de Octubre
Madrid, 280 41
- Withdrawn
Hospital Universitario Vithas Madrid La Milagrosa
Madrid, 28010
- Withdrawn
Hospital Regional Universitario de Málaga
Málaga, 29010
- Withdrawn
Hospital Clinico Universitario de Valladolid
Valladolid, 47003
- Active, not recruiting
Hospital Clinico Viña del Mar
Valparaíso, 2520612
Argentina4 sites, 1 recruiting
- Withdrawn
Hospital General de Agudos J.M. Ramos Mejia
Buenos Aires, 1221
- Recruiting
STAT Research S.A.
Buenos Aires, C1023AAB
- Withdrawn
Hospital Italiano
Buenos Aires, C1181ACH
- Active, not recruiting
Sanatorio del Sur S.A
San Miguel de Tucumán, 4000
Austria4 sites, 4 recruiting
- Recruiting
University Hospital Innsbruck
Innsbruck, 6020
- Recruiting
Universitaetsklinik fuer Kinder
Linz, 4021
- Recruiting
Universitätsklinik für Neurologie
Salzburg, 5020
- Recruiting
Universitätsklinik für Neurologie, Medizinische Universität Wien
Vienna, 1090
Canada4 sites, 4 recruiting
- Recruiting
Center for Neurologic Research
Lethbridge, Alberta, T1J 0N9
- Recruiting
London Health Sciences Center
London, Ontario, N6A5A5
- Recruiting
Le Centre Hospitalier de l'Universite' de Montreal (CHUM)
Montreal, Quebec, H2X 0C1
- Recruiting
Children and Women's Health Centre of BC (BC Children's Hospital)
Vancouver, British Columbia, V6H 3V4
Israel4 sites, 4 recruiting
- Recruiting
Hadassah University Medical Center
Jerusalem, 9112001
- Recruiting
The Chaim Sheba Medical Center
Ramat Gan, 6265601
- Recruiting
Kaplan Medical Center
Rehovot, 7661041
- Recruiting
The Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
Bulgaria3 sites, 2 recruiting
- Recruiting
Multiprofile hospital for active treatment Puls AD
Blagoevgrad, 2700
- Recruiting
MHATNP 'Sveti Naum' EAD
Sofia, 1113
- Withdrawn
First University Multiprofile Hospital for Active Treatment Sofia Sv. Joan Krastitel
Sofia, 1142
Croatia3 sites
- Withdrawn
Clinical Hospital Center Osijek
Osijek, 310 00
- Withdrawn
Clinical Hospital Center Rijeka
Rijeka, 510 00
- Withdrawn
University Hospital Center Zagreb
Zagreb, 100 00
Mexico3 sites
- Active, not recruiting
Grupo Medico Camino SC
Mexico City, 03310
- Active, not recruiting
Human Science Research Trials S. de R.L. de C.V.
Mexico City, 14050
- Active, not recruiting
Neurociencias Estudios Clínicos S.C
Sinaloa, 80020
Belgium2 sites, 2 recruiting
- Recruiting
Cliniques Universitaires Saint-Luc
Brussels, 1200
- Recruiting
Universitair Ziekenhuis Gent
Ghent, 9000
Chile1 site
- Active, not recruiting
Centro de investigación Clinica UC-CICUC
Santiago
Czechia1 site
- Withdrawn
Fakultni nemocnice v Motole Neurologicka klinika 2. LF UK a FN Motol
Prague, 150 06
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 Primary Generalized Tonic-Clonic Seizures
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).
Read the detailed description
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.
- Being tested
- XEN1101, Placebo
- Keywords
- Epilepsy
- Medical subject headings
- 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 monthly (28 days) PGTCS frequency
Median percent change (MPC) in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo.
Measured: Baseline through DBP (Week 12)
Secondary outcomes (2)
Proportion of subjects
Proportion of subjects experiencing ≥50% reduction in monthly (28 days) PGTCS frequency from baseline through the DBP for XEN1101 versus placebo.
Measured: Baseline through DBP (Week 12)
Proportion of subjects
Proportion of subjects experiencing PGTCS freedom from baseline through the DBP for XEN1101 versus placebo.
Measured: Baseline through Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2022
- Study start14 Feb 2023
- Primary completionApr 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Generalized Tonic-Clonic 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
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xenon Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Worldwide Clinical Trials
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Xenon Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05667142
- Sponsor's protocol ID
- XPF-010-303
- Other IDs
- 2022-502286-16-00
- Acronym
- X-ACKT
- Status last verified
- Oct 2026
- First submitted
- 19 Dec 2022
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No