XEN1101 for Epilepsy

(X-TOLE4 Trial)

Recruiting at 144 trial locations

Overseen By Xenon Pharmaceuticals Inc.

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Xenon Pharmaceuticals Inc.

Disqualifiers: Medical condition, Experimental device, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 2

Duration: Up to 3 years

880 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, XEN1101, to evaluate its safety and effectiveness for people with certain types of seizures, such as Focal Onset Seizures or Primary Generalized Tonic-Clonic Seizures. The researchers aim to understand the drug's long-term effects over a period of up to three years. Suitable participants have already taken part in a previous study with XEN1101 and can maintain an accurate seizure diary. As a Phase 3 trial, this represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

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

Research has shown that XEN1101 has promising safety results from past studies. In earlier trials, XEN1101 was tested for focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS). These studies found that patients generally tolerated it well, with most side effects being mild to moderate. Importantly, no serious side effects were directly linked to the medication in the available data.

In a study where XEN1101 was used as an additional treatment, patients tolerated it well over a long period, allowing continued use without major problems. While all medications can have some side effects, current data suggest that XEN1101 is generally safe.

Overall, the evidence supports the safety of XEN1101 for treating seizures, though ongoing research aims to confirm these findings over the long term. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

XEN1101 is unique because it targets epilepsy by modulating potassium channels in the brain, which is a different approach compared to many traditional anti-seizure medications that primarily focus on sodium channels or GABA receptors. This new mechanism of action could offer a fresh avenue for patients who don't respond well to existing treatments like carbamazepine or valproate. Researchers are excited about XEN1101 because it has the potential to reduce seizure frequency more effectively and with fewer side effects, offering hope to those with hard-to-treat epilepsy.

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

Research has shown that XEN1101, also known as Azetukalner, could significantly aid in treating epilepsy, particularly for Focal Onset Seizures (FOS). Previous studies found that XEN1101 becomes more effective for FOS with increased doses. It targets specific potassium channels in the brain, which are crucial in controlling seizures. Long-term data also support its safety and effectiveness, indicating it could be a promising option for those experiencing seizures. ^{1 2 3 5 6}

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 with Focal Onset Seizures or Primary Generalized Tonic-Clonic Seizures who have completed a previous study without early termination or significant issues. Participants must be able to follow the study's instructions, keep accurate seizure diaries, and provide informed consent.

Inclusion Criteria

Subject must have successfully completed the DBP and have not terminated early from Study X-TOLE2, X-TOLE3, or X-ACKT, met all eligibility requirements, and had no important protocol deviations (in the opinion of the sponsor) or AEs (in the opinion of the investigator) that would preclude the subject's entry into the long-term extension study.

In the opinion of the investigator, the subject is able to understand verbal and written instructions and will adhere to all study schedules and requirements.

Subject is able to keep accurate seizure diaries.

Exclusion Criteria

Subject has any medical condition, personal circumstance, or ongoing AE (from Study X-TOLE2, X-TOLE3, or X-ACKT) 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 am not planning to join another drug study or use an experimental device for my epilepsy or any other condition during this study and for 28 days after.

Subject met any of the withdrawal criteria while in Study X-TOLE2, X-TOLE3, or X-ACKT.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Not specified

Treatment

Participants receive XEN1101 for the treatment of seizures, with visits at 2-, 4-, and 13-weeks post-entry, and subsequent visits at 13-week intervals during the first year, then at 26-week intervals with a telephone call in between

Up to 3 years

Visits at 2, 4, 13 weeks, then every 13 weeks for the first year, and every 26 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XEN1101

Trial Overview The trial is testing the long-term safety and effectiveness of XEN1101, taken orally once daily at a dose of 25 mg. It aims to treat seizures in patients with certain types of epilepsy over a period of up to three years.

How Is the Trial Designed?

Group I: XEN1101 15 or 25 mg/day Experimental Treatment 1 Intervention

XEN1101 15 or 25 mg/day

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+

Citations

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

Targeting Kv7 Potassium Channels for Epilepsy - PMC In a cardiac study in healthy subjects, a mean QT prologation of 7.7 ms was observed at 3 h after dosing at a dose of 400 mg t.i.d. [104]. Azetukalner (XEN1101).

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. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05614063

NCT05614063 | A Randomized Study of XEN1101 Versus ... A randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive ...

5. 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 ...

6. 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 ...