XEN1101 for Seizures

(X-TOLE2 Trial)

Not currently recruiting at 167 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called XEN1101 to determine its effectiveness for people with focal-onset seizures. Researchers aim to assess its efficacy, safety, and tolerability as an additional therapy. Participants will receive either a placebo (inactive substance) or varying doses of XEN1101. Those diagnosed with focal epilepsy for at least two years, who have not achieved sustained seizure freedom despite trying at least two anti-seizure medications, are suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that XEN1101 is generally well-tolerated. In earlier studies, some participants experienced side effects, but most were mild to moderate. Common issues included dizziness or drowsiness. However, these side effects did not prevent most participants from continuing treatment. Long-term studies indicate that XEN1101 does not cause serious harm.

The current trial's advanced stage suggests that substantial safety information already exists for this treatment. XEN1101 has been tested in previous trials and found to be relatively safe. For those considering joining a trial, it is reassuring to know that others have already used the treatment without major safety problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for seizures?

Unlike standard seizure medications that often target neurotransmitter systems, XEN1101 is unique because it acts on potassium channels in the brain. This distinct mechanism of action could offer better seizure control with potentially fewer side effects. Researchers are excited because XEN1101 might provide a new option for patients who don't respond well to other treatments, and its innovative approach could lead to faster onset of action.

What evidence suggests that XEN1101 might be an effective treatment for seizures?

Research has shown that XEN1101 might help with focal-onset seizures. XEN1101 opens certain potassium channels in the brain, calming the overactive brain activity that causes seizures. In this trial, participants will receive either XEN1101 at different dosages or a placebo. Studies with previous patients have demonstrated that the drug is more effective at higher doses. Early results indicated that XEN1101 significantly reduced the number of seizures compared to a placebo. This evidence suggests that XEN1101 could be a promising option for those seeking better seizure control. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Xenon Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37812429/

Efficacy and Safety of XEN1101, a Novel Potassium ... To evaluate the efficacy and safety of XEN1101, a novel small-molecule selective Kv7.2/Kv7.3 potassium channel opener, in the treatment of focal-onset seizures ...

2. trial.medpath.com trial.medpath.com/drug/report/9fc177f1b9b46acc

Azetukalner | Advanced Drug Monograph - MedPath In epilepsy, Azetukalner has demonstrated robust, dose-dependent efficacy in a Phase 2b trial for FOS.[4] More compellingly, long-term data from ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11850491/

Targeting Kv7 Potassium Channels for Epilepsy - PMC Voltage-gated Kv7 potassium channels, particularly Kv7.2 and Kv.7.3 channels, play a critical role in modulating susceptibility to seizures.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05716100

A Randomized Study of XEN1101 Versus Placebo in Focal ... 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 ...

5. xenon-pharma.com xenon-pharma.com/wp-content/uploads/2024/04/xen1101-clinical-trial-brochure.pdf

XEN1101 Clinical Trial Brochure A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Safety and. Efficacy of XEN1101 as an Adjunctive Therapy in the Treatment of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05716100

NCT05716100 | A Randomized Study of XEN1101 Versus ... Median percent change (MPC) in focal seizure frequency from baseline to DBP for XEN1101 versus placebo. From baseline through to the double blind period (week ...

7. aesnet.org aesnet.org/abstractslisting/long-term-safety-and-efficacy-of-azetukalner-a-novel-potent-kv7-potassium-channel-opener-in-adults-with-focal-epilepsy-update-from-the-ongoing-7-year-open-label-extension-of-x-tole

long-term safety and efficacy of azetukalner, a novel, potent ... Rationale: Azetukalner (XEN1101) is in development as a treatment for epilepsy ... safety and efficacy data using a data cut from April 2024.