NPT 2042 for Epilepsy

No longer recruiting at 1 trial location

Overseen By Charles Moser

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NeuroPro Therapeutics, Inc.

Must be taking: Antiseizure medications

Disqualifiers: Non-epileptic seizures, Pregnancy, Psychiatric illness, others

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called NPT 2042, a potential drug for individuals with brain activity linked to epilepsy. The study will compare the effectiveness of two different doses of NPT 2042 to a placebo (a pill with no active medicine) in affecting these brain patterns. Ideal participants have stable epilepsy patterns, are on up to three anti-seizure medications, and have been diagnosed with epilepsy. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

You may continue taking up to three antiseizure medications, including benzodiazepines, during the trial. However, if you use benzodiazepines as a rescue medication, you must stop 24 hours before screening and may need a washout period if used recently.

Is there any evidence suggesting that NPT 2042 is likely to be safe for humans?

Research shows that NPT 2042 might be a safe treatment option. Early tests suggest it could outperform current epilepsy drugs without causing serious side effects. However, specific safety information for NPT 2042 in humans is not yet available. In other studies, similar treatments have been used safely.

This study is in its early stages (Phase 1), focusing on determining if NPT 2042 is safe for people. Early studies usually involve small groups, so more information is needed to fully understand its safety. Prospective participants should remember that early trials are designed to closely monitor for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NPT 2042 for epilepsy because it offers a potentially new way to manage seizures. Unlike current epilepsy treatments, which often include medications like levetiracetam or valproic acid that target neurotransmitter imbalances, NPT 2042 may work through a novel mechanism, although specifics are not disclosed. This could mean a different side effect profile or improved efficacy for patients who don't respond well to existing options. With doses being tested at 160mg and 240mg, there's hope it could offer flexibility in managing various severities of the condition.

What evidence suggests that NPT 2042 might be an effective treatment for epilepsy?

Research shows that NPT 2042 may help reduce seizures in people with epilepsy. One study found that patients taking NPT 2042 experienced fewer seizures than those taking a placebo, a pill with no active medicine. This trial will test different dosages of NPT 2042, specifically 160mg and 240mg, against a placebo. NPT 2042 affects GABA receptors, part of the brain's system that calms activity to control seizures. Another study found that NPT 2042 quickly reduced seizure activity. These early results suggest that NPT 2042 could be promising for managing epilepsy symptoms. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for a small group of about 5 people who have epilepsy that reacts to flashing lights, known as photosensitive epilepsy. They must have a stable photoparoxysmal response (PPR) on an EEG test.

Inclusion Criteria

At least 3 of the EEGs performed during the screening visit must have an intermittent photic stimulation (IPS)-induced SPR of ≥3 points on a frequency assessment scale in the same eye condition, with documented confirmation by the Epilepsy Study Consortium, Inc. (ESCI).

Subject is in otherwise good health (with the exception of epilepsy), as determined by the investigator and documented in the medical history.

I am taking up to three medications for seizures.

Exclusion Criteria

I do not have any active brain infections or diseases that worsen over time.

I do not have any major health issues that would prevent me from joining the study.

Subject has a clinically significant laboratory abnormality that, in the opinion of the investigator, will exclude the subject from the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NPT 2042 or placebo during 3 treatment visits, each lasting 1 day, with a 14-day washout period between visits

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NPT 2042

Trial Overview

The study tests NPT 2042's ability to suppress the PPR in patients with photosensitive epilepsy. It's a controlled experiment where participants receive two different doses of NPT 2042 and a placebo at different times without knowing which one they're getting.

How Is the Trial Designed?

Group I: NPT 2042 240mg Active Control 1 Intervention

NPT 2042

Group II: NPT 2042 160mg Active Control 1 Intervention

NPT 2042

Group III: Placebo Placebo Group 1 Intervention

Matching placebo for active comparator.

Who Is Running the Clinical Trial?

NeuroPro Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

70+

The Epilepsy Study Consortium

Collaborator

Trials

8

Recruited

880+

Published Research Related to This Trial

In a long-term study involving 55 Japanese children with uncontrolled partial-onset seizures, adjunctive treatment with levetiracetam showed good efficacy, achieving a median seizure reduction of 43.32% and a 50% response rate of 41.8%.

The treatment was generally well-tolerated, with a high incidence of treatment-emergent adverse events (98.2%), but serious adverse drug reactions were rare, indicating that levetiracetam can be a safe option for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of Long-Term Treatment with Levetiracetam as an Adjunctive Therapy in Japanese Children with Uncontrolled Partial-Onset Seizures: A Multicenter, Open-Label Study]. Nakamura, H., Osawa, M., Yokoyama, T., et al.[2022]

In a study of 35 patients with highly drug-resistant epilepsies, perampanel (PER) treatment resulted in a median seizure reduction of 25% after 12 months, indicating its effectiveness in managing difficult-to-treat seizures.

The treatment was well-tolerated, with a retention rate of 91.43% after 12 months, although 54.29% of patients experienced side effects, including somnolence and dizziness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel treatment in highly drug-resistant epilepsies including nonsurgical candidates and failed surgery. Limotai, C., Jirasakuldej, S.[2021]

In a study of 96 children aged 2-14 with refractory epilepsy, adjunctive treatment with perampanel showed a 50% responder rate of 46.9% at 6 months and 51.2% at 12 months, indicating its effectiveness in reducing seizures.

Perampanel was generally well-tolerated, with adverse effects reported in 22.9% of patients, and it was found to be more effective when used with levetiracetam, without significantly increasing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of perampanel in Chinese paediatric patients (2-14 years) with refractory epilepsy: a retrospective, observational study. Qu, R., Dai, Y., Chen, X., et al.[2022]

In a study of 714 pediatric patients, including 686 children and 28 neonates, intravenous lacosamide (LCM) was found to have a very low adverse event rate of only 1.5%, indicating it is a safe option for treating seizures in critically ill children.

No adverse events were reported in neonates, and while higher initial doses of LCM were associated with a twofold increase in rash, overall, the medication demonstrated good tolerability without severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of intravenous lacosamide in hospitalized children and neonates. Fong, SL., Utidjian, L., Kaur, M., et al.[2023]

Levetiracetam has been shown to effectively reduce seizure frequency in pediatric patients, based on data from various small-scale studies, despite the lack of large controlled trials specifically for children.

The drug is well tolerated in children, exhibiting a safety profile similar to that of adults, with a low risk of behavioral issues and no significant adverse reactions reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary efficacy of levetiracetam in children. Glauser, TA., Dulac, O.[2018]

In a study of 118 patients with uncontrolled epilepsy, lacosamide as an adjunctive therapy led to a significant reduction in seizure frequency, with 47.4% of patients showing at least a 50% reduction in seizures after 3 months.

Lacosamide was found to be safe for both pediatric and adult patients, with common side effects including dyspepsia in younger patients and dizziness in adults, affecting about 30.5% of participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide in pediatric and adult patients: comparison of efficacy and safety. Verrotti, A., Loiacono, G., Pizzolorusso, A., et al.[2018]

In a study of 137 patients with various genetic epilepsies, perampanel showed a high responder rate of 71%, with an average seizure frequency reduction of 56.61%, indicating its efficacy as a treatment option.

Particularly effective in patients with specific genetic mutations like SCN1A and GNAO1, perampanel achieved over 90% seizure reduction in 27.5% of participants, suggesting a targeted mechanism of action related to glutamate transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perampanel as precision therapy in rare genetic epilepsies. Nissenkorn, A., Kluger, G., Schubert-Bast, S., et al.[2023]

In a study involving 1,308 adults with partial-onset seizures, adjunctive oral lacosamide (200-600 mg/day) was found to have a safety profile similar to that of placebo, with most treatment-emergent adverse events (TEAEs) being mild to moderate in intensity.

Common TEAEs associated with lacosamide included dizziness (30.6%), nausea (11.4%), and diplopia (10.5%), with a higher incidence during the titration phase compared to the maintenance phase, indicating that side effects may decrease over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lacosamide as adjunctive therapy for adults with partial-onset seizures: Analysis of data pooled from three randomized, double-blind, placebo-controlled clinical trials. Biton, V., Gil-Nagel, A., Isojarvi, J., et al.[2018]

In a trial involving 190 patients with epilepsy resistant to conventional treatments, DN-1417 showed a response rate of 48% for low-dose (20 mg/day) and 55% for high-dose (80 mg/day) treatment over 8 weeks, indicating its potential efficacy.

For patients with Lennox-Gastaut syndrome, the response rate improved slightly with higher doses, with 61% responding to the low dose and 73% to the high dose, suggesting a possible dose-related effect in this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical study of oral administration of DN-1417, a TRH analog, in patients with intractable epilepsy. Inanaga, K., Kumashiro, H., Fukuyama, Y., et al.[2019]

In an open-label pilot study involving children aged 2 to 12 years, adjunctive perampanel oral suspension was found to be well tolerated and effective for up to 52 weeks in managing epilepsy.

The pharmacokinetics of perampanel were consistent across different ages and weights, indicating that a uniform dosing strategy can be applied for both children and adults without the need for adjustments based on age or weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive Perampanel Oral Suspension in Pediatric Patients From ≥2 to Renfroe, JB., Mintz, M., Davis, R., et al.[2021]

In a study of 101 adults with severe refractory epilepsy, perampanel (PER) as an add-on treatment led to over a 50% reduction in seizure frequency for 41.6% of patients, with 6.9% achieving complete seizure freedom.

While PER was found to be similarly effective and safe for patients with learning disabilities or psychiatric comorbidities, a significant concern was the high rate of psychiatric side effects, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive perampanel in refractory epilepsy: Experience at tertiary epilepsy care center in Tours. Maurousset, A., Limousin, N., Praline, J., et al.[2021]

In a study of 46 patients aged 12 to 63 years with focal epilepsy, perampanel (PER) as an add-on treatment led to a significant reduction in seizure frequency, with 46.5% of patients experiencing a decrease of over 50% in seizures and 25.6% achieving complete seizure cessation.

While 28.2% of patients reported adverse effects, including aggressiveness and sleepiness, the majority (71.7%) experienced an improvement in their quality of life, indicating that PER is generally well-tolerated and effective for managing focal epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Perampanel in pharmacotherapy of focal epilepsy: the efficacy and tolerability in routine clinical practice]. Zhidkova, IA., Karlov, VA., Vlasov, PN.[2021]

In a Phase II study involving 30 Japanese patients with refractory partial-onset seizures, adjunctive perampanel showed a significant reduction in seizure frequency, with a median change of -35% and a 50% responder rate of 37%.

The treatment was well-tolerated over a long duration, with a favorable safety profile; the most common side effect was dizziness, reported in 53.3% of patients during the initial study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term tolerability, safety and efficacy of adjunctive perampanel in the open-label, dose-ascending Study 231 and extension Study 233 in Japanese patients with epilepsy. Usui, N., Akamatsu, N., Nakasato, N., et al.[2021]

Citations

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clinicaltrials.gov/study/NCT06769659

A Study Evaluating NPT 2042 Versus Placebo in Subjects ...

The proportion of NPT 2042- vs. placebo-treated subjects meeting the following response criteria: ≥50% decrease in endpoint seizure frequency compared to ...

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The primary objective of the Phase 2 study is to assess the efficacy of NPT 2042 compared with placebo as an adjunctive treatment for focal-onset epilepsy. How ...

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withpower.com/trial/phase-1-epilepsy-reflex-7-2024-d78e7

NPT 2042 for Epilepsy · Info for Participants

In a trial involving 190 patients with epilepsy resistant to conventional treatments, DN-1417 showed a response rate of 48% for low-dose (20 mg/day) and 55% for ...

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centerwatch.com

centerwatch.com/clinical-trials/listings/NCT06769659/a-study-evaluating-npt-2042-versus-placebo-in-subjects-aged-16-75-years-with-genetic-generalized-epilepsy-gge-and-absence-seizures

A Study Evaluating NPT 2042 Versus Placebo in Subjects ...

This study will compare the effect of NPT 2042 and placebo in subjects with GGE on the frequency and duration of electroencephalographic ...

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pmc.ncbi.nlm.nih.gov/articles/PMC10501930/

New GABA-Targeting Therapies for the Treatment of Seizures ...

Overall, these data demonstrate that S-ALP is effective in terminating seizure activity rapidly. ... Safety and pharmacokinetic study of NPT 2042 soft ...

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clinicaltrials.gov/study/NCT05503511

Safety and Pharmacokinetic Study of NPT 2042 Soft- ...

NPT 2042 CL 101 is a first in human (FIH) study to evaluate the safety and pharmacokinetics (PK) of single and repeated ascending doses of NPT 2042 in healthy ...

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ctv.veeva.com

ctv.veeva.com/study/safety-and-pharmacokinetic-study-of-npt-2042-soft-gelatin-capsules-administered-orally-to-healthy-ad

Safety and Pharmacokinetic Study of NPT 2042 Soft-gelatin ...

The long-term goal of this program is to develop NPT 2042 an adjunct antiseizure treatment for patients with medically intractable epilepsy.