NPT 2042 for Epilepsy

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

9 Participants Needed

Trial Summary

What is the purpose of this trial?

A double-blind, placebo-controlled, crossover trial to investigate the PPR of approximately 5 subjects with a known stable PPR on EEG, using 2 doses of NPT 2042 compared to placebo.

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.

What data supports the effectiveness of the drug NPT 2042 for epilepsy?

The study on DN-1417, a similar treatment, showed that 48% of patients with difficult-to-treat epilepsy improved with a low dose, and 55% improved with a high dose. This suggests that treatments like NPT 2042 might also help reduce seizures in patients with epilepsy. ^{1 2 3 4 5}

What safety data exists for NPT 2042 or similar treatments?

There is no specific safety data available for NPT 2042, but similar treatments like lacosamide and levetiracetam have been studied. Lacosamide has been shown to be safe in both children and adults with seizures, while levetiracetam is well tolerated in children with a safety profile similar to adults. ^{6 7 8 9 10}

How is the drug NPT 2042 different from other epilepsy treatments?

NPT 2042 is unique because it is being studied for its effectiveness in patients with epilepsy that does not respond to conventional treatments, and it is administered orally once a day while fasting. This approach is different from other treatments like perampanel, which is used as an add-on therapy and targets specific receptors in the brain. ^{1 2 11 12 13}

Eligibility Criteria

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

I am taking up to three medications for seizures.

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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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 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 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]

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 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]

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]

References

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

Clinical study of oral administration of DN-1417, a TRH analog, in patients with intractable epilepsy. [2019]

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

Adjunctive Perampanel Oral Suspension in Pediatric Patients From ≥2 to [2021]

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

Perampanel treatment in highly drug-resistant epilepsies including nonsurgical candidates and failed surgery. [2021]

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

Adjunctive perampanel in refractory epilepsy: Experience at tertiary epilepsy care center in Tours. [2021]

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

Effectiveness and safety of perampanel in Chinese paediatric patients (2-14 years) with refractory epilepsy: a retrospective, observational study. [2022]

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

Safety of intravenous lacosamide in hospitalized children and neonates. [2023]

7. Japan 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]. [2022]

8. United States 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. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Lacosamide in pediatric and adult patients: comparison of efficacy and safety. [2018]

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

Preliminary efficacy of levetiracetam in children. [2018]

11. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Perampanel in pharmacotherapy of focal epilepsy: the efficacy and tolerability in routine clinical practice]. [2021]

12. England 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. [2021]

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

Perampanel as precision therapy in rare genetic epilepsies. [2023]