What is the mechanism of action of this treatment?

Common treatments for epilepsy work through various mechanisms to stabilize neuronal activity and prevent seizures. These include sodium channel blockers (e.g., carbamazepine, phenytoin), which reduce neuronal excitability; GABA enhancers (e.g., valproic acid, benzodiazepines), which increase inhibitory neurotransmission; and calcium channel blockers (e.g., ethosuximide), which reduce excitatory neurotransmission. Potassium channel modulators, like XEN1101, work by enhancing the activity of potassium channels, leading to hyperpolarization of neurons and reduced excitability. Understanding these mechanisms is crucial for epilepsy patients as it helps in selecting the most effective treatment with the least side effects, tailored to their specific type of epilepsy and individual response to medication.

What side effects are associated with this type of intervention?

Common treatments for epilepsy include antiepileptic drugs (AEDs) such as carbamazepine, levetiracetam, and valproate. Potassium channel modulators like XEN1101 are being studied for their efficacy and safety. Known side effects of these treatments can include dizziness, fatigue, nausea, and cognitive disturbances. Specific to potassium channel modulators, potential side effects may also include somnolence, headache, and mood changes. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of epilepsy, including those that act on various mechanisms. While specific potassium channel modulators like XEN1101 are still under study, other approved treatments include lamotrigine, valproate, and levetiracetam, which have shown efficacy in clinical trials. These drugs work through different mechanisms, such as sodium channel inhibition and modulation of neurotransmitter release, to control seizures. Additionally, newer treatments like fenfluramine have been approved for specific epilepsy syndromes like Dravet syndrome, offering more options for patients with refractory epilepsy.

What other types of research exist?

Promising novel alternatives to XEN1101 for epilepsy treatment include: 1. Cannabidiol (CBD) - Shown efficacy in Dravet syndrome and Lennox-Gastaut syndrome. 2. Ganaxolone - Positive results in CDKL5 deficiency disorder. 3. Lacosamide - Effective as monotherapy in newly diagnosed epilepsy. 4. Levetiracetam - Proven efficacy in various epilepsy syndromes. 5. Quinidine - Limited but potential use in KCNT1 associated epilepsy.

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XEN1101 for Epilepsy (X-TOLE Trial)

Phase 2

Waitlist Available

Research Sponsored by Xenon Pharmaceuticals Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

Seizures secondary to other diseases or conditions

History of pseudoseizures, psychogenic seizures, primary generalized seizure, or focal aware non-motor seizures only

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline (8 weeks prior to day 0) through to the final dose (up to day 56)

Awards & highlights

Summary

This trial tests XEN1101, a new medication, in adults with focal epilepsy who still have seizures despite taking other anti-epileptic drugs. The goal is to see if XEN1101 can better control their seizures by working with their current medications.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects are not detailed here but generally could include typical drug reactions such as skin rashes (like Stevens-Johnson syndrome), blood issues (hematological reactions), organ toxicity, and other medication-related allergies.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My seizures are caused by another health condition.

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I have a history of seizures that are not caused by a physical condition.

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I have used vigabatrin but my vision tests were not stable after stopping it.

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I have a heart condition that affects my heartbeat's timing.

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I have been on felbamate for 2 years with a stable dose for the last 2 months and have normal blood and liver tests.

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I have had skin or eye issues due to ezogabine.

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I have or had Lennox-Gastaut syndrome.

Select...

I do not have schizophrenia, other psychotic disorders, recent suicidal thoughts or attempts.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline (8 weeks prior to day 0) through to the final dose (up to day 56)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline (8 weeks prior to day 0) through to the final dose (up to day 56)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline (8 weeks prior to day 0) through to the final dose (up to day 56) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To assess the efficacy of XEN1101 compared to placebo on focal seizure frequency (e.g., median percent change in focal seizure frequency) in adults with focal epilepsy taking 1-3 antiepileptic drugs (AEDs) in the double-blind treatment period (DBP)

To assess the safety and tolerability of XEN1101 (e.g., adverse events) in adults with focal epilepsy taking 1-3 AEDs

Secondary study objectives

To evaluate the 50% XEN1101 response rates in comparison to placebo in the DBP

To evaluate trends in focal seizure frequency over time in the DBP

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: 25 mg XEN1101Experimental Treatment1 Intervention

Capsule filled with 25 mg XEN1101

Group II: 20 mg XEN1101Experimental Treatment1 Intervention

Capsule filled with 20 mg XEN1101

Group III: 10 mg XEN1101Experimental Treatment1 Intervention

Capsule filled with 10 mg XEN1101

Group IV: PlaceboPlacebo Group1 Intervention

Placebo capsule

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for epilepsy work through various mechanisms to stabilize neuronal activity and prevent seizures. These include sodium channel blockers (e.g., carbamazepine, phenytoin), which reduce neuronal excitability; GABA enhancers (e.g., valproic acid, benzodiazepines), which increase inhibitory neurotransmission; and calcium channel blockers (e.g., ethosuximide), which reduce excitatory neurotransmission. Potassium channel modulators, like XEN1101, work by enhancing the activity of potassium channels, leading to hyperpolarization of neurons and reduced excitability. Understanding these mechanisms is crucial for epilepsy patients as it helps in selecting the most effective treatment with the least side effects, tailored to their specific type of epilepsy and individual response to medication.

Anticonvulsant drugs: mechanisms of action.