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Evaluating XEN1101 for treating primary generalized tonic-clonic seizures

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

PHASE3 · Xenon Pharmaceuticals Inc. · NCT05667142

This study is testing a new medication called XEN1101 to see if it can help people aged 12 and older with primary generalized tonic-clonic seizures who are still having seizures despite taking other medications.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment160 (estimated)
Ages12 Years and up
SexAll
SponsorXenon Pharmaceuticals Inc. (industry)
Locations138 sites (Mobile, Alabama and 137 other locations)
Trial IDNCT05667142 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial is designed to assess the efficacy, safety, and tolerability of XEN1101 as an adjunctive therapy for patients with primary generalized tonic-clonic seizures (PGTCS). Participants aged 12 years and older, who have not achieved seizure freedom despite taking 1 to 3 anti-seizure medications, will be randomly assigned to receive either XEN1101 or a placebo for 12 weeks. The study will include a double-blind treatment period followed by an optional open-label extension for those who complete the initial phase. The trial aims to gather comprehensive data on seizure frequency and overall patient well-being.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 12 years and older with a diagnosis of generalized epilepsy and a history of primary generalized tonic-clonic seizures.

Not a fit: Patients who have not previously tried at least two anti-seizure medications or those with other types of epilepsy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients struggling to control their seizures with existing medications.

How similar studies have performed: Previous studies have shown promise with similar adjunctive therapies for epilepsy, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Mobile, Alabama and 137 other locations

+88 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Primary Generalized Tonic-Clonic Seizures, Epilepsy

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.