XEN1101 for Partial Seizures

Recruiting at 63 trial locations

Overseen By Xenon Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Xenon Pharmaceuticals Inc.

Must be taking: Antiseizure medications

Disqualifiers: Generalized seizures, Psychogenic seizures, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

360 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of 1 to 3 of your current seizure medications for at least one month before starting and throughout the study.

What makes the drug XEN1101 unique for treating partial seizures?

XEN1101 is unique because it is a novel treatment option for partial seizures, potentially offering a different mechanism of action compared to traditional antiepileptic drugs, although specific details about its mechanism are not provided in the available research. ^{1 2 3 4 5}

Research Team

Xenon Medical Director

Principal Investigator

Xenon Pharmaceuticals Inc.

Eligibility Criteria

This trial is for adults with focal epilepsy diagnosed at least 2 years ago, who've tried and not responded to at least two anti-seizure medications (ASMs). They must be on a stable dose of 1-3 ASMs currently. Participants need to provide informed consent, have no history of certain non-focal seizures or neurosurgery within specific time frames, and can't have seizures from other medical conditions.

Inclusion Criteria

I have been on 1 to 3 approved seizure medications for at least a month.

You can accurately keep track of your seizures in a diary.

Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study

Exclusion Criteria

I do not have seizures caused by substance use, infections, cancer, or other listed conditions.

I have had uncountable seizures or status epilepticus in the last year.

I had neurosurgery for seizures less than a year ago or radiosurgery less than two years ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Assessment of seizure frequency over a period of up to 9.5 weeks

9.5 weeks

Treatment

Participants receive XEN1101 or placebo once daily for 12 weeks

12 weeks

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment with XEN1101 long-term

Treatment Details

Interventions

• Placebo
• XEN1101

Trial Overview The X-TOLE3 study tests the effectiveness and safety of XEN1101 as an additional treatment for focal-onset seizures compared to a placebo. It's randomized (participants are assigned by chance) and double-blind (neither participants nor researchers know who gets what), ensuring unbiased results.

Participant Groups

Group I: XEN1101 25 mg/day Experimental Treatment 1 Intervention

XEN1101 25 mg/day

Group II: XEN1101 15 mg/day Experimental Treatment 1 Intervention

XEN1101 15 mg/day

Group III: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Xenon Pharmaceuticals Inc.

Lead Sponsor

Trials

19

Recruited

3,400+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Findings from Research

Xanthotoxin (XANT) significantly enhances the anticonvulsant effects of levetiracetam and valproate, reducing their effective doses needed to prevent seizures in a mouse model, indicating its potential as a co-treatment for epilepsy.

XANT does not negatively affect motor coordination or memory, suggesting it is safe to use alongside these antiepileptic drugs, while it increases the brain concentration of valproate, indicating a pharmacokinetic interaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xanthotoxin enhances the anticonvulsant potency of levetiracetam and valproate in the 6-Hz corneal stimulation model in mice. Zagaja, M., Bryda, J., Szewczyk, A., et al.[2022]

IEM-2062 demonstrates a strong anticonvulsant effect in a rat model, completely preventing kindling in 100% of cases and significantly reducing the severity of seizures, outperforming traditional treatments like memantine and sodium valproate.

IEM-2062 is much safer than these conventional drugs, causing locomotor disturbances only at doses 30.7 times higher than those needed for its maximum anticonvulsant effect, indicating a better safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[COMPARISON OF CHRONIC ANTICONVULSANT ACTIVITY AND SAFETY OF IEM-2062, SODIUM VALPROATE AND ME-MANTINE IN THE PENTYLENETETRAZOL KINDLING MODEL IN RATS]. Gmiro, VE., Serdyuk, SE., Veselkina, OS.[2018]

Phenobarbital (PB) was found to be more effective in suppressing seizures in the hippocampal-kindled model compared to the amygdaloid-kindled model, indicating that the location of seizure activity in the brain significantly influences drug efficacy.

In the hippocampal-kindled group, PB effectively suppressed generalized convulsions at serum levels of 15-25 micrograms/ml, while amygdaloid-kindled seizures showed resistance to PB, suggesting that the challenges in treating temporal lobe epilepsy may be linked to the specific brain regions involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Different effects of chronically administered phenobarbital on amygdaloid- and hippocampal-kindled seizures in the cat]. Sumi, T.[2013]

In a study of five neonates with KCNQ2/3-related seizures, recognizing a specific aEEG pattern allowed for early treatment with carbamazepine (CBZ), which was effective in all four patients treated with it.

Neonates with a continuous normal voltage background and sleep-wake cycling showed better developmental outcomes, while those not treated with CBZ had higher seizure burdens and worse developmental results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinctive Amplitude-Integrated EEG Ictal Pattern and Targeted Therapy with Carbamazepine in KCNQ2 and KCNQ3 Neonatal Epilepsy: A Case Series. Vilan, A., Grangeia, A., Ribeiro, JM., et al.[2023]

Loss of normal PSEN2 function in mice is linked to age-dependent changes in susceptibility to seizures, indicating that genetic factors may play a significant role in seizure activity in Alzheimer's disease.

The study suggests that using established models of chronic seizures in aged rodents can help understand how age affects seizure susceptibility and the effectiveness of antiseizure drugs, potentially improving treatment strategies for seizures in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loss of presenilin 2 age-dependently alters susceptibility to acute seizures and kindling acquisition. Beckman, M., Knox, K., Koneval, Z., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Xanthotoxin enhances the anticonvulsant potency of levetiracetam and valproate in the 6-Hz corneal stimulation model in mice. [2022]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[COMPARISON OF CHRONIC ANTICONVULSANT ACTIVITY AND SAFETY OF IEM-2062, SODIUM VALPROATE AND ME-MANTINE IN THE PENTYLENETETRAZOL KINDLING MODEL IN RATS]. [2018]

3. Japan pubmed.ncbi.nlm.nih.gov

[Different effects of chronically administered phenobarbital on amygdaloid- and hippocampal-kindled seizures in the cat]. [2013]

4. Germany pubmed.ncbi.nlm.nih.gov

Distinctive Amplitude-Integrated EEG Ictal Pattern and Targeted Therapy with Carbamazepine in KCNQ2 and KCNQ3 Neonatal Epilepsy: A Case Series. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Loss of presenilin 2 age-dependently alters susceptibility to acute seizures and kindling acquisition. [2021]