Perampanel for Status Epilepticus

Overseen By Kelly Jia

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wayne State University

Must not be taking: CYP3A4 inducers, PMP

Disqualifiers: Pregnancy, Hepatic impairment, Renal impairment, Psychiatric illness, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 months

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Perampanel, a drug that blocks overactive brain signals, to help patients with severe seizures that don't respond to other treatments. The study aims to see if this drug can effectively and safely control these difficult-to-treat seizures.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications, but it advises caution if you are taking certain drugs like carbamazepine, oxcarbazepine, phenytoin, or other strong CYP3A4 inducers.

What data supports the effectiveness of the drug Perampanel (Fycompa) for treating status epilepticus?

Perampanel has shown effectiveness in controlling seizures in epilepsy, and animal studies suggest it may help with status epilepticus, a severe type of seizure. ^{1 2 3 4 5}

Is Perampanel safe for humans?

Perampanel, also known as Fycompa, has been studied in thousands of patients with epilepsy and is generally well tolerated. Common side effects include dizziness, sleepiness, and tiredness. ^{1 2 3 6 7}

How is the drug Perampanel unique in treating status epilepticus?

Perampanel is unique because it is a first-in-class drug that works by blocking AMPA receptors, which reduces excessive brain activity linked to seizures. It is taken once daily and has shown promise in treating refractory status epilepticus, a severe form of seizures that is difficult to control with other treatments. ^{1 2 8 9 10}

Research Team

Wazim Mohamed, MD

Principal Investigator

Wayne State University

Maysaa Basha, MD

Principal Investigator

Wayne State University

Eligibility Criteria

Adults over 18 with refractory status epilepticus (RSE), which is a type of seizure that doesn't stop after treatment with first and second-line medications. Participants must not be pregnant, have severe liver or kidney issues, anoxic brain injury as the cause of RSE, or take certain other drugs that affect how Perampanel works.

Inclusion Criteria

I have severe epilepsy that didn't stop after two types of medication.

I use oral contraception and am open to discussing other methods.

Exclusion Criteria

I am cautious with medications that affect liver enzymes, like some seizure drugs.

My seizures are due to a lack of oxygen to the brain.

I have liver problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive perampanel for the treatment of refractory status epilepticus, with clinical evaluations and administration of the study drug

6 months

2 visits (in-person) at 3 and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of seizure control and functional outcomes

6 months

Follow-up assessments at 3 and 6 months

Long-term follow-up

Participants' outcomes are evaluated for long-term safety and effectiveness, including seizure control and functional status

Up to 96 weeks

Treatment Details

Interventions

• Perampanel

Trial Overview The trial tests Perampanel's effectiveness and safety in treating RSE at WSU for about 96 weeks. It includes initial screening, medical history review, physical and neurological exams, followed by two clinic visits. Patient data will be collected to identify outcome determinants.

Participant Groups

Group I: Single arm prospective study Experimental Treatment 1 Intervention

* Adults patients equal or greater than 18 years * Patients in RSE that require IV anesthetic infusions. Note: RSE is defined as status epilepticus that fails to terminate after an adequate dose of benzodiazepines (1st line agents) and an AED (2nd line agent). Adequate doses have been defined in the screening (below). * Patients taking oral contraception who will be on the study long term should be informed about additional alternative methods of contraception.

Perampanel is already approved in European Union, United States for the following indications:

Approved in European Union as Fycompa for:

• Partial-onset epilepsy (with or without secondary generalized seizures)
• Primary generalized tonic-clonic seizures

Approved in United States as Fycompa for:

• Partial-onset seizures (with or without secondary generalized seizures)
• Primary generalized tonic-clonic seizures
• Monotherapy and adjunctive therapy for focal epilepsy (with or without secondary generalized seizures) in patients aged 4 years and older

Who Is Running the Clinical Trial?

Wayne State University

Lead Sponsor

Trials

318

Recruited

111,000+

Findings from Research

Perampanel has been shown to be effective in reducing seizure frequency in patients with epilepsy, demonstrating significant clinical efficacy in multiple studies.

The safety profile of perampanel indicates that while it is generally well-tolerated, it can cause side effects such as dizziness and fatigue, which should be monitored in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel (Fycompa): A Review of Clinical Efficacy and Safety in Epilepsy. Greenwood, J., Valdes, J.[2020]

Perampanel is a newly approved antiepileptic drug in the EU, specifically indicated for use as an additional treatment for partial-onset seizures in patients aged 12 and older.

It is designed to be used alongside other medications, highlighting its role as an adjunctive therapy in managing epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel: a new add-on treatment for epilepsy. [2021]

In the FAME study, perampanel was effective in reducing seizure frequency in patients with focal-onset seizures, with the highest efficacy observed at a low dose of 4 mg/day, regardless of the specific seizure type.

While treatment-emergent adverse events (TEAEs) were more common during the initial 12-week titration period (60.2%) compared to the 24-week maintenance period (28.4%), most TEAEs were self-limited or well-tolerated, indicating a favorable safety profile for perampanel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel as First Adjunctive Treatment in Patients with Focal-Onset Seizures in the FAME Study: Post hoc Analyses of Dose-Related Efficacy, Safety and Clinical Factors Associated with Response. Kim, DW., Kim, JH., Lee, SK., et al.[2022]

In a study of 77 patients with focal-onset seizures, perampanel (PER) as an early add-on therapy resulted in a 60% reduction in seizure frequency for over half of the participants after 12 months, with a retention rate of 79.2%.

PER was particularly effective for patients experiencing focal to bilateral tonic-clonic seizures, achieving a 60% seizure-free rate, although 40.3% of patients reported mild adverse events, leading to a 15.6% discontinuation rate due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel effectiveness and safety as early add-on treatment for focal-onset seizures: PEREAGAL study. Rodríguez-Osorio, X., Lema-Facal, T., Rubio-Nazábal, E., et al.[2022]

In a 52-week observational study involving 483 patients with refractory epilepsy, perampanel was found to have a safety profile consistent with previous clinical studies, with 62.3% of patients reporting at least one treatment-emergent adverse event (TEAE), primarily mild to moderate in severity.

The most common clinically important TEAEs included dizziness (13.9%) and balance disorders (5.6%), with 31.7% of patients experiencing such events, indicating that while perampanel is effective, monitoring for these side effects is essential in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-approval observational study to evaluate the safety and tolerability of perampanel as an add-on therapy in adolescent, adult, and elderly patients with epilepsy. Maguire, M., Ben-Menachem, E., Patten, A., et al.[2022]

Perampanel is an effective adjunctive treatment for patients aged 12 and older with primary generalized tonic-clonic seizures and partial-onset seizures, showing significant improvements in seizure control during phase III trials lasting 17 to 19 weeks, and sustained control for up to 4 years in some cases.

The drug is generally well tolerated, with most side effects being mild to moderate and related to the central nervous system, such as dizziness and fatigue, making it a viable option for patients with drug-resistant seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel: A Review in Drug-Resistant Epilepsy. Frampton, JE.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Perampanel (Fycompa): A Review of Clinical Efficacy and Safety in Epilepsy. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Perampanel: a new add-on treatment for epilepsy. [2021]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Perampanel as First Adjunctive Treatment in Patients with Focal-Onset Seizures in the FAME Study: Post hoc Analyses of Dose-Related Efficacy, Safety and Clinical Factors Associated with Response. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Perampanel effectiveness and safety as early add-on treatment for focal-onset seizures: PEREAGAL study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Perampanel in the treatment of status epilepticus: A systematic review of the literature. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Perampanel in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A post-approval observational study to evaluate the safety and tolerability of perampanel as an add-on therapy in adolescent, adult, and elderly patients with epilepsy. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Perampanel in achieving status epilepticus cessation: A systematic review. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Perampanel Treatment for Refractory Status Epilepticus in a Neurological Intensive Care Unit. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Perampanel: A Review in Drug-Resistant Epilepsy. [2021]