XEN1101 for Seizures

(X-TOLE2 Trial)

Recruiting at 151 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: Non-epileptic seizures, Generalized 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-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.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial requires that you continue taking a stable dose of 1 to 3 allowable anti-seizure medications (ASMs) for at least one month before and throughout the study.

How does the drug XEN1101 differ from other treatments for seizures?

XEN1101 is unique because it is a novel potassium channel modulator, which means it works by targeting specific channels in the brain to stabilize nerve cell activity and prevent seizures. This mechanism of action is different from many traditional antiepileptic drugs that often target sodium channels or neurotransmitter systems. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Xenon Pharmaceuticals Inc.

Eligibility Criteria

This trial is for individuals diagnosed with focal epilepsy for at least 2 years, who have tried at least two anti-seizure medications without success. Participants must be on a stable dose of 1 to 3 permitted seizure medicines and able to maintain accurate seizure diaries. It's not suitable for those with seizures due to other health issues or substance use, or those who've had recent neurosurgery.

Inclusion Criteria

I have had focal epilepsy for 2+ years and two medications haven't stopped my seizures.

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

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

Exclusion Criteria

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.

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

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Assessment of seizure frequency over a baseline period

9.5 weeks

Treatment

Participants receive XEN1101 or placebo once daily for 12 weeks

12 weeks

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-TOLE2 Phase 3 study tests the effectiveness and safety of XEN1101 as an additional treatment for focal-onset seizures compared to a placebo. Participants are randomly assigned to receive either XEN1101 or a placebo in addition to their current seizure medications.

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

In a rat model of microgyria, zolpidem showed decreased efficacy on inhibitory neurotransmission in lesioned brain tissue, indicating altered GABA receptor function that may relate to delayed maturation in these neurons.

Ifenprodil increased the threshold for triggering epileptiform discharges in lesioned cortex, suggesting that changes in NMDA receptor subunit expression contribute to heightened sensitivity in this model of cortical dysplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered receptor subunit expression in rat neocortical malformations. Hablitz, JJ., DeFazio, RA.[2019]

In a study involving rats, Panax ginseng demonstrated significant antiepileptic activity by reducing the occurrence of seizures induced by pentylenetetrazole (PTZ), suggesting its potential as a treatment for epilepsy.

Rats treated with Panax ginseng at a dose of 100 mg/kg showed improved seizure protection compared to the control group, indicating its efficacy in preventing generalized tonic-clonic convulsions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptic activity of Panax ginseng against pentylenetetrazole induced kindling in rats. Gupta, YK., Sharma, M., Chaudhary, G.[2014]

Zonisamide has been shown to be effective in treating refractory partial seizures in adults, with doses of 300 mg/day or higher leading to significant reductions in seizure frequency, particularly at 500 mg/day where a 51% reduction was observed compared to placebo.

The drug has an excellent safety and tolerability profile, with most adverse events being mild to moderate and a low rate of discontinuation, making it a suitable option for patients when used alongside other antiepileptic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zonisamide as adjunctive therapy for refractory partial seizures. Brodie, MJ.[2018]

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]

In a pilot study involving 12 adult male patients with difficult-to-control seizures, nafimidone demonstrated significant efficacy, with 8 patients showing a 33-98% improvement in seizure control during a 2-week treatment period.

Long-term follow-up revealed that 6 out of 10 patients maintained a 53% to over 99% improvement in seizure frequency over 46-53 weeks, suggesting nafimidone's potential as a long-term treatment option for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of nafimidone in the treatment of intractable partial seizures: report of a two-center pilot study. Treiman, DM., Wilensky, AJ., Ben-Menachem, E., et al.[2019]

References

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

Altered receptor subunit expression in rat neocortical malformations. [2019]

2. India pubmed.ncbi.nlm.nih.gov

Antiepileptic activity of Panax ginseng against pentylenetetrazole induced kindling in rats. [2014]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Zonisamide as adjunctive therapy for refractory partial seizures. [2018]

4. 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]

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

Efficacy of nafimidone in the treatment of intractable partial seizures: report of a two-center pilot study. [2019]