XEN1101 for Epilepsy

(X-TOLE Trial)

Not currently recruiting at 115 trial locations

Overseen By NCGS, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Xenon Pharmaceuticals Inc.

Must be taking: AEDs

Must not be taking: Vigabatrin, Felbamate

Disqualifiers: Schizophrenia, Psychotic disorders, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called XEN1101 for individuals with focal epilepsy, where seizures begin in one part of the brain. The study aims to evaluate the effectiveness of different XEN1101 doses in reducing seizures and to assess its safety. Participants will receive either XEN1101 or a placebo (a capsule with no active medicine). Suitable candidates are adults who have had focal epilepsy for at least two years and are on a stable dose of 1 to 3 anti-seizure medications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

No, you won't have to stop taking your current medications. The trial requires that you continue taking a stable dose of 1 to 3 allowable anti-epileptic drugs (AEDs) throughout the study.

Is there any evidence suggesting that XEN1101 is likely to be safe for humans?

Research has shown that XEN1101 is generally safe for people with focal epilepsy. This treatment helps open certain channels in the brain and has undergone testing in several studies. These studies evaluate its safety and effectiveness in treating seizures.

Reports from the studies indicate that side effects are usually mild, with common ones including dizziness, headaches, and fatigue. Most people find these side effects manageable. It's important to note that XEN1101 remains under investigation, and ongoing studies continue to assess its safety.

For those considering joining a trial, this information may provide reassurance about the treatment's safety. However, discussing any concerns with a healthcare provider is essential. ^{1 2 3 4 5}

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

Researchers are excited about XEN1101 for epilepsy because it offers a fresh approach in managing seizures. Unlike many current treatments that focus on altering neurotransmitter levels, XEN1101 works by enhancing the activity of potassium channels in the brain. This mechanism helps stabilize the brain's electrical activity, potentially reducing the frequency and severity of seizures. By targeting these specific channels, XEN1101 aims to provide effective seizure control with possibly fewer side effects, making it a promising option for patients who may not respond well to existing medications like levetiracetam or lamotrigine.

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

Research has shown that XEN1101, a new medication, may help treat focal epilepsy. This trial will test different doses of XEN1101—10 mg, 20 mg, and 25 mg—to evaluate their effectiveness in reducing seizures. Studies have found that higher doses can lead to fewer seizures. XEN1101 works by opening certain pathways in the brain, calming the overactive signals that cause seizures. Patients have generally tolerated it well, with few serious side effects reported. Overall, this treatment could offer a new option for people with focal epilepsy. ^{1 3 4 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Xenon Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

Adults with a diagnosis of focal epilepsy for at least 2 years, BMI ≤40 kg/m2, on stable doses of 1-3 approved AEDs can join. They must have had prior neuroimaging and be able to keep seizure diaries. Exclusions include history of certain non-focal seizures, recent neurosurgery, psychotic disorders or suicide risk, significant medical conditions like long QT syndrome or cancer within the past two years.

Inclusion Criteria

I agree not to donate sperm/ova during the study and for 6 months after.

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

I have been on 1 to 3 epilepsy drugs at a stable dose for at least a month.

Exclusion Criteria

I have had severe allergic reactions to epilepsy drugs.

My seizures are caused by another health condition.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants' seizure frequency is assessed over an 8-week period

8 weeks

Treatment

Participants receive XEN1101 or placebo once daily in the evening for 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Open-label extension (optional)

Eligible participants receive a 20 mg daily dose of XEN1101

What Are the Treatments Tested in This Trial?

Interventions

• XEN1101

Trial Overview The trial is testing XEN1101 as an additional treatment for focal epilepsy in adults. It's a randomized study where patients either get XEN1101 or a placebo without knowing which one they're getting. After that phase, there's an optional part where everyone gets XEN1101.

How Is the Trial Designed?

Group I: 25 mg XEN1101 Experimental Treatment 1 Intervention

Capsule filled with 25 mg XEN1101

Group II: 20 mg XEN1101 Experimental Treatment 1 Intervention

Capsule filled with 20 mg XEN1101

Group III: 10 mg XEN1101 Experimental Treatment 1 Intervention

Capsule filled with 10 mg XEN1101

Group IV: Placebo Placebo Group 1 Intervention

Placebo capsule

Who Is Running the Clinical Trial?

Xenon Pharmaceuticals Inc.

Lead Sponsor

Trials

19

Recruited

3,400+

NCGS, Inc.

Industry Sponsor

Trials

2

Recruited

620+

Novotech Health Holdings Pte. Ltd.

Industry Sponsor

Trials

1

Recruited

330+

Novotech Health Holdings Pte. Ltd.

Collaborator

Trials

1

Recruited

330+

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10562989/

Efficacy and Safety of XEN1101, a Novel Potassium Channel ... Treatment with XEN1101 was associated with a statistically significant and robustly dose-dependent decrease in monthly seizure frequency and was generally well ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05667142

NCT05667142 | A Study to Evaluate XEN1101 as ... This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of XEN1101

4. 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 and major depressive disorder. In a randomized, double-blind ...

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

XEN1101 Clinical Trial Brochure Rapid Onset of Efficacy of XEN1101, a Novel Potassium Channel Opener, in. Adults with Focal Epilepsy: Results from a Phase 2b Study (X-TOLE). European ...

6. link.springer.com link.springer.com/article/10.1007/s40263-024-01155-3

Targeting Kv7 Potassium Channels for Epilepsy | CNS Drugs 2/3 openers, azetukalner (XEN 1101) is currently in phase III development for the treatment focal seizures, generalized tonic-clonic seizures ...