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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of perampanel (Fycompa) for individuals with status epilepticus, a seizure type unresponsive to usual treatments. The goal is to determine if perampanel is a safe and effective option for those whose seizures haven't responded to other medicines. The study will also gather information to understand factors that might influence patient outcomes on this treatment. This trial may suit adults whose status epilepticus persists despite other medications and who require IV anesthetic infusions. As a Phase 4 trial, this research focuses on understanding how this already FDA-approved treatment can benefit more patients.

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 is the safety track record for Perampanel?

Research has shown that perampanel is generally safe for people with status epilepticus, a severe type of seizure. Studies have found it effective in stopping seizures for many patients and that it is usually well-tolerated. In one study, perampanel stopped seizures in all patients, with only one person experiencing severe restlessness.

These findings suggest that perampanel is a relatively safe option for treating status epilepticus. However, like any treatment, it can have side effects, so discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for status epilepticus, which typically involve benzodiazepines and other anti-epileptic drugs, Perampanel offers a unique approach. It works by selectively targeting AMPA receptors in the brain, which play a key role in the excessive neuronal firing seen in seizures. This mechanism of action sets it apart from the usual treatments that generally act on different pathways. Researchers are excited because this could mean a more targeted way to control seizures that don't respond to existing medications, potentially offering hope for patients who have limited options.

What evidence suggests that perampanel might be an effective treatment for status epilepticus?

Research has shown that perampanel can help treat refractory status epilepticus (RSE), a severe type of seizure that doesn't respond to usual treatments. Studies have found that perampanel is safe and effective in stopping seizures when other treatments fail. Specifically, one study reported that about 36.5% of patients with RSE stopped having seizures after using perampanel. Another study found it particularly effective for certain seizures, with success rates up to 66.7% for focal motor seizures. Overall, perampanel appears to be a promising option for those who haven't responded to other treatments. Participants in this trial will receive perampanel to evaluate its effectiveness in treating RSE. ^{2 3 6 7 8}

Who Is on the Research Team?

Maysaa Basha, MD

Principal Investigator

Wayne State University

Wazim Mohamed, MD

Principal Investigator

Wayne State University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10819860/

Efficacy of Perampanel in Refractory and ... - PubMed Central (4) Conclusions: Our data support the efficacy of PER in treating SE when first- and second-line ASMs have failed and suggest a possible earlier ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33754209/

Efficacy and safety of perampanel in refractory and super- ... Perampanel is effective and has a satisfactory safety profile in the emergency treatment of established RSE and SRSE.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525505025003956

Efficacy and safety of perampanel in critically ill pediatric ... The overall response rate was 40.6 %, highest in the focal motor SE group (8/12, 66.7 %) compared to the generalized tonic-clonic seizures (3/10, 30.0 %) and ...

4. epilepsybehavior.com epilepsybehavior.com/article/S1525-5050(22)00032-4/abstract

Perampanel in achieving status epilepticus cessation Perampanel has been shown to work in lithium-pilocarpine models. Perampanel was given at 2–32 mg between 30 min and 51 days from status epilepticus onset.

5. neurology.org neurology.org/doi/10.1212/WNL.92.15_supplement.P3.5-005

Perampanel Use in Established, Refractory, and Super ... The rate of seizure cessation attributed to perampanel treatment (36.5%) in this refractory and heterogeneous population represents a notable ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39436521/

Effectiveness and safety of Perampanel in refractory status ... Results: Perampanel was successful in terminating SE in all the described cases. Only in one patient a severe psychomotor agitation occurred, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525505024002075

Use of perampanel oral suspension for the treatment ... Full-dose patients showed higher response rate while maintaining safety. Abstract. Introduction. Status epilepticus (SE) is a medical emergency associated with ...

8. aesnet.org aesnet.org/abstractslisting/the-efficacy-and-safety-of-perampanel-use-in-patients-with-refractory-status-epilepticus-at-a-single-center-in-the-united-arab-emirates-(uae)

The-Efficacy-and-Safety-of-Perampanel-Use-in-Patients-with ... The average maintenance dose was 8 mg. PER was found to have definite improvement in 4/10 (40%) patients. Of those (75%) became seizure free.