Clinical Trials for Generalised Tonic-Clonic Seizures

There are currently 6 ongoing clinical trials investigating new treatments for generalised tonic-clonic seizures. These studies are testing medications such as vormatrigine (PRAX-628), XEN1101, and cenobamate to help reduce seizure frequency and improve quality of life for patients. Trials are taking place across multiple countries in Europe, and participants include adults and, in some studies, adolescents aged 12 and older.

Clinical trial locations

• Austria
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Belgium
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Bulgaria
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Croatia
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Czechia
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Finland
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• France
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Germany
  • Study of PRAX-628 to evaluate safety and effectiveness in adults with epilepsy who have focal seizures or generalized tonic-clonic seizures
  • Study on PRAX-628 for Adults with Focal Onset or Generalized Tonic-Clonic Seizures
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
  • Study on the Effectiveness and Safety of Cenobamate for Patients Aged 12 and Older with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety of Cenobamate for Patients with Primary Generalized Tonic-Clonic Seizures
• Hungary
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
  • Study on the Effectiveness and Safety of Cenobamate for Patients Aged 12 and Older with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety of Cenobamate for Patients with Primary Generalized Tonic-Clonic Seizures
• Ireland
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Italy
  • Study of PRAX-628 to evaluate safety and effectiveness in adults with epilepsy who have focal seizures or generalized tonic-clonic seizures
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Latvia
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Netherlands
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Poland
  • Study of PRAX-628 to evaluate safety and effectiveness in adults with epilepsy who have focal seizures or generalized tonic-clonic seizures
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
  • Study on the Effectiveness and Safety of Cenobamate for Patients Aged 12 and Older with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety of Cenobamate for Patients with Primary Generalized Tonic-Clonic Seizures
• Portugal
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
• Slovakia
  • Study on the Effectiveness and Safety of Cenobamate for Patients Aged 12 and Older with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety of Cenobamate for Patients with Primary Generalized Tonic-Clonic Seizures
• Spain
  • Study of PRAX-628 to evaluate safety and effectiveness in adults with epilepsy who have focal seizures or generalized tonic-clonic seizures
  • Study on PRAX-628 for Adults with Focal Onset or Generalized Tonic-Clonic Seizures
  • Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures
  • Study on the Effectiveness and Safety of Cenobamate for Patients Aged 12 and Older with Primary Generalized Tonic-Clonic Seizures
  • Study on the Long-term Safety of Cenobamate for Patients with Primary Generalized Tonic-Clonic Seizures

Study of PRAX-628 to evaluate safety and effectiveness in adults with epilepsy who have focal seizures or generalized tonic-clonic seizures

This trial is studying vormatrigine in adults with epilepsy who experience either focal onset seizures or primary generalized tonic-clonic seizures. The main goal is to determine how safe and well-tolerated this investigational medication is when given to patients who have previously received it in other clinical trials or through special access programs.

Inclusion criteria: Participants must be adults aged 18 or older with a diagnosis of either focal onset seizures or primary generalized tonic-clonic seizures. They must have previously participated in specific vormatrigine trials or received the medication through approved programs, demonstrating good compliance with keeping a seizure diary and taking medication as directed. Participants must be willing to sign informed consent, follow all study procedures, and use appropriate contraception during the study.

Exclusion criteria: The study excludes people under 18 or over 65 years old, pregnant or breastfeeding women, and those with allergies to similar medications. Individuals with seizure types other than focal onset or primary generalized tonic-clonic, severe kidney or liver problems, uncontrolled high blood pressure, or major psychiatric disorders cannot participate. Those with a history of drug or alcohol abuse within the past two years, currently participating in other trials, or unable to follow study procedures are also excluded.

Study focus: Throughout the treatment period of up to 24 months, doctors will monitor participants’ health through vital sign checks, blood tests, electrocardiograms, and mental health assessments. Participants will maintain a seizure diary to track frequency, and both patients and doctors will evaluate the severity of the condition using specific scales. Blood samples will measure medication levels, and any side effects will be carefully recorded and monitored.

Investigational drug: Vormatrigine is an oral medication taken in capsule form. It works by modulating neuronal sodium channels to reduce excessive electrical activity in the brain, potentially helping control both focal seizures and primary generalized tonic-clonic seizures in adult patients.

Study on PRAX-628 for Adults with Focal Onset or Generalized Tonic-Clonic Seizures

This trial evaluates PRAX-628’s effectiveness in reducing seizure frequency in adults with focal onset seizures or primary generalized tonic-clonic seizures. The study lasts up to eight weeks, with participants continuing their usual anti-seizure medications while adding PRAX-628 to their treatment plan.

Inclusion criteria: Participants must be between 18 and 75 years old with a diagnosis of focal onset seizures, focal onset to bilateral generalized seizures, or primary generalized tonic-clonic seizures. They must have had a CT or MRI scan showing their epilepsy isn’t caused by a progressive condition. Participants must be taking a stable dose of one to three anti-seizure medications for at least four weeks before the study. They must have experienced at least two countable focal onset seizures per month or one countable generalized tonic-clonic seizure per month in the three months prior. During the screening period, they must record at least two countable seizures (focal) or one (generalized) and complete their seizure diary on at least 80% of days.

Exclusion criteria: People not currently taking anti-seizure medications cannot participate. Those with seizure types other than focal onset or primary generalized tonic-clonic are excluded, as are those outside the age range or unable to give informed consent.

Study focus: The trial begins with a screening period to monitor baseline seizure frequency, followed by a treatment period where participants take PRAX-628 orally in capsule form. The dosage is adjusted based on individual response and side effects. Throughout the study, participants’ health is monitored through vital signs, laboratory tests, and electrocardiograms. The impact is evaluated using specific scales, and the incidence and severity of side effects are recorded. At the end, seizure frequency is compared to the baseline to determine effectiveness.

Investigational drug: PRAX-628 is an oral medication being tested for its ability to reduce seizure frequency in adults already taking other anti-seizure medications. It works by modulating specific ion channels in the brain to stabilize neuronal activity and prevent seizures.

Study on the Effects of XEN1101 and Placebo for Patients with Primary Generalized Tonic-Clonic Seizures

This double-blind trial studies XEN1101’s ability to reduce the frequency of primary generalized tonic-clonic seizures when used alongside other treatments. Participants are randomly assigned to receive either XEN1101 or a placebo for a 12-week period.

Inclusion criteria: Participants must be at least 12 years old with probable or possible primary generalized tonic-clonic seizures for at least one year, confirmed by specific medical guidelines and approved by the study committee. They must have tried at least two different seizure medications at proper doses without achieving long-term freedom from seizures, and seizures must have started before age 40. Participants must be on a stable dose of one to three allowed seizure medications for at least one month. They must have had a routine electroencephalogram within five years and a brain scan within ten years, and experienced at least three seizures in the eight weeks before the study. If using devices like vagal nerve stimulators, these must have been implanted at least five months prior with stable settings. Participants must be able to keep accurate seizure records and follow the study’s birth control requirements.

Exclusion criteria: The trial excludes those without primary generalized tonic-clonic seizures, people outside the age range, and those unwilling or unable to follow study procedures. Pregnant or breastfeeding women, individuals with significant health issues that might interfere, current participants in other trials, those with a history of drug or alcohol abuse, people who have had recent major surgery, and those with known allergies to the study medication cannot participate.

Study focus: After providing written consent and undergoing initial assessment, participants enter a baseline period to establish seizure frequency while continuing current treatments. Following randomization, they take the assigned medication orally in capsule form during the treatment phase, continuing to record seizure activity. Regular follow-up visits monitor health, assess treatment effectiveness, and address any side effects. A final assessment is conducted at the end of the study.

Investigational drug: XEN1101 is an oral medication taken in tablet form. It works by targeting specific channels in the brain that help control electrical activity, aiming to reduce seizure frequency. The medication is classified as an anticonvulsant and is currently in Phase 3 clinical trials.

Study on the Long-term Safety and Tolerability of Azetukalner for Patients with Epilepsy, Including Focal-onset and Primary Generalized Tonic-Clonic Seizures

This open-label trial evaluates the long-term safety and tolerability of XEN1101 in people with epilepsy, including those with focal-onset and primary generalized tonic-clonic seizures. The study monitors participants until September 2028 to gather important information about extended medication use.

Inclusion criteria: Participants must have completed previous study periods (Study XPF-010-301, XPF-010-302, or XPF-010-303) without leaving early and met all necessary requirements, with no major issues or side effects that would prevent joining this long-term study. They must be able to keep accurate seizure records and fully understand the study’s nature and risks. Participants must agree to follow birth control rules, with males agreeing not to donate sperm until three months after the last dose and females not donating eggs until six months after. They should be able to understand spoken and written instructions and follow all study schedules and requirements.

Exclusion criteria: People who haven’t completed the specified previous studies cannot participate. Those outside the specified age range, without the specific seizure types being studied, or considered part of a vulnerable population are excluded.

Study focus: Participants take XEN1101 orally in capsule form with dosage and frequency determined by the study protocol. Throughout the long-term evaluation, regular assessments monitor safety and tolerability, including tracking side effects and health changes. Participants maintain seizure diaries to record frequency and severity. The study evaluates changes in seizure frequency over time, comparing baseline rates to each four-week assessment period, along with changes in quality of life and other health-related measures.

Investigational drug: XEN1101 is administered orally and works by modulating potassium channels in the brain to stabilize neuronal activity and reduce seizure frequency. It is classified as an anticonvulsant currently being studied for its long-term safety in treating epilepsy.

Study on the Effectiveness and Safety of Cenobamate for Patients Aged 12 and Older with Primary Generalized Tonic-Clonic Seizures

This trial studies cenobamate’s effectiveness and safety when used alongside other treatments for primary generalized tonic-clonic seizures in patients aged 12 and older. Participants receive either cenobamate or a placebo over several months to determine if the medication can reduce seizure frequency and improve quality of life.

Inclusion criteria: Participants must be males or females at least 12 years old with a medical diagnosis of primary generalized tonic-clonic seizures, possibly along with other types of generalized seizures. They must have had at least five seizures in the 12 weeks before the study starts and an electroencephalogram within the last five years showing signs of idiopathic generalized epilepsy. A CT scan or MRI within the last ten years must show no worsening cause of epilepsy. Participants must be taking one to three antiepileptic drugs with stable doses for at least 30 days. If using benzodiazepines at least once weekly, it counts as one drug, and the dose shouldn’t change during the study. If using a vagal nerve stimulator or deep brain stimulator, it must have been in place for at least five months with stable settings for 30 days before and during the study. Those on a ketogenic diet must maintain it stably for three months before and during the study. Participants or their legal guardians must sign informed consent, and females who can have children must use reliable birth control.

Exclusion criteria: Individuals under 12 years old cannot participate. Those without primary generalized tonic-clonic seizures, unable to follow study procedures or take medication as required, with other interfering medical conditions, pregnant or breastfeeding, currently in another trial, with a history of drug or alcohol abuse, or who have had allergic reactions to the study medication or similar medications are excluded.

Study focus: Participants are randomly assigned to receive cenobamate or placebo in a double-blind fashion. During the titration phase, dosing begins at 12.5 mg per day and gradually increases over several weeks to reach 200 mg per day (or equivalent for adolescents). The medication is taken orally as film-coated tablets or oral suspension. Once the target dose is reached, participants continue through a maintenance phase while monitoring seizure frequency to assess effectiveness. A follow-up period evaluates long-term effects and any potential side effects.

Investigational drug: Cenobamate is administered orally in tablet form. It works by modulating sodium channels and enhancing GABAergic inhibition to stabilize neuronal activity. While approved in some regions for partial-onset seizures, this trial evaluates its broader applications as an adjunctive therapy for primary generalized tonic-clonic seizures.

Study on the Long-term Safety of Cenobamate for Patients with Primary Generalized Tonic-Clonic Seizures

This trial evaluates the long-term safety and tolerability of cenobamate as an additional therapy for people with primary generalized tonic-clonic seizures. The study continues until December 2026, monitoring participants who have completed the previous double-blind treatment period.

Inclusion criteria: Participants must have successfully completed the double-blind treatment period in the core study. Written informed consent is required from the participant or their legal guardian following international guidelines. If a legal guardian signs the consent, the patient must also give their agreement, either in writing or verbally. The study is open to both males and females, including those considered part of a vulnerable population.

Exclusion criteria: Patients with seizure types different from primary generalized tonic-clonic, those outside the specified age range (children, teenagers, and adults), unable to follow study procedures or take medication as required, with other interfering medical conditions, pregnant or breastfeeding, taking certain interfering medications, with a history of drug or alcohol abuse, or who have recently participated in another clinical trial cannot participate.

Study focus: Participation begins after completing the previous study phase. Cenobamate is available in different forms and dosages: 10mg/mL oral suspension and tablets of 12.5mg, 25mg, and 50mg. The medication is taken orally with specific dosage and frequency determined by the study team based on individual needs and responses. Regular monitoring ensures safety through checking vital signs, conducting physical and neurological examinations, performing electrocardiograms, and laboratory tests to monitor health status. The study design evaluates long-term safety as long as participation is beneficial and safe according to study guidelines.

Investigational drug: Cenobamate is administered orally in tablet form. It works by modulating ion channels in the brain to stabilize neuronal activity and prevent seizures. The medication is classified as an anticonvulsant being evaluated for its long-term safety and effectiveness in managing seizure disorders.

Summary

The six ongoing clinical trials for generalised tonic-clonic seizures represent significant research efforts across Europe, with Germany, Poland, and Spain hosting the most trials. Three distinct investigational medications are being evaluated: vormatrigine (PRAX-628), XEN1101, and cenobamate. Notably, two trials focus on vormatrigine, two on XEN1101 for long-term safety and effectiveness, and two on cenobamate examining both initial effectiveness and long-term safety.

The trials vary in their participant age ranges, with most studies focusing on adults aged 18 and older, while some cenobamate trials include adolescents as young as 12 years old. Several studies are examining long-term safety and tolerability, reflecting the importance of understanding how these medications perform over extended periods. Most trials require participants to already be taking stable doses of existing anti-seizure medications, positioning these investigational drugs as additional therapies rather than replacements.

A common feature across the trials is the requirement for participants to maintain detailed seizure diaries, demonstrating the importance of accurate seizure tracking in evaluating treatment effectiveness. The geographic distribution shows a concentration in Central and Western Europe, with Croatia, Portugal, Czechia, Austria, Italy, Bulgaria, Netherlands, France, Belgium, Slovakia, Latvia, Ireland, Hungary, and Finland also participating as trial sites.