LP352 for Epilepsy

Recruiting at 174 trial locations

Overseen By Longboard Study Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Longboard Pharmaceuticals

Must be taking: Antiseizure medications

Must not be taking: Cannabis products

Disqualifiers: Dravet syndrome, Neurodegenerative disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 7

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LP352, a potential drug for managing seizures in people with certain types of epilepsy. It targets individuals with Lennox-Gastaut Syndrome (LGS) or other developmental and epileptic encephalopathies (DEE), where seizures began by age 8 or 5, respectively, along with developmental challenges. Participants who frequently experience multiple types of seizures and are on a stable medication plan might be suitable candidates. The study compares LP352 to a placebo to evaluate its effectiveness and safety over time. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on a stable dose of 1 to 4 antiseizure medications for at least 4 weeks before the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that LP352 is likely to be safe for humans?

Research has shown that LP352 is generally safe for people. Studies have found it works well with other medications and causes few interactions, benefiting those taking multiple drugs. An ongoing study is examining its long-term safety to ensure it remains safe for extended use. Overall, evidence suggests LP352 is safe for treating seizures, but discussing any new treatment with a healthcare provider is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

LP352 is unique because it targets epilepsy in a novel way by modulating serotonin receptors, which is different from most standard treatments that typically focus on sodium channels or GABA receptors. This new mechanism of action could potentially offer better control over seizures with fewer side effects. Researchers are excited about LP352 because it represents a fresh approach that may improve quality of life for patients who don't respond well to current medications like valproate or carbamazepine.

What evidence suggests that LP352 might be an effective treatment for epilepsy?

Research has shown that LP352, which participants in this trial may receive, may help reduce seizures. One study found that LP352 lowered brain seizure activity by an average of 69.1%. Another study reported that over half of the participants taking LP352 experienced at least a 50% reduction in seizures. Compared to a placebo group, those taking LP352 had a median seizure reduction of 53.3%, while the placebo group only saw a 20.8% reduction. These results suggest that LP352 could effectively reduce seizures in developmental and epileptic conditions. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children and adults with Developmental and Epileptic Encephalopathies (DEE), a group of conditions that include severe forms of epilepsy. Participants must meet specific health criteria to join, but the exact inclusion and exclusion details are not provided here.

Inclusion Criteria

I have been on 1 to 4 seizure medications for at least 4 weeks without changing the dose.

I was diagnosed with Lennox-Gastaut Syndrome, had seizures before age 8, developmental issues, and specific EEG results.

I had seizures start before I was 6, have had different types of seizures, and my development has stalled or reversed.

Exclusion Criteria

I have a brain disorder confirmed by scans or genetic tests.

I have a brain injury or lesion that could cause seizures, not related to my main condition.

I was hospitalized and needed a breathing machine for a severe seizure within the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants are titrated up to the highest tolerated dose of LP352

4 weeks

Visits 2 to 5

Maintenance

Participants maintain the highest tolerated dose of LP352

6 weeks

Visits 5 to 8

Taper

Participants undergo tapering or down titration of LP352

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LP352

Trial Overview The study tests LP352, a potential new treatment for seizures in DEE patients. It's compared against a placebo over several phases: Screening, Titration (dose adjustment), Maintenance, Taper period (gradual dose reduction), and Follow-Up, spanning about 24 months.

How Is the Trial Designed?

Group I: LP352 Experimental Treatment 1 Intervention

Participants will be titrated up to highest tolerated dose of LP352 during the Titration period (Visit 2 - Visit 5), followed by maintenance period (Visit 5 - Visit 8) and then taper/down titration period.

Group II: Placebo Placebo Group 1 Intervention

Placebo for LP352

Who Is Running the Clinical Trial?

Longboard Pharmaceuticals

Lead Sponsor

Trials

5

Recruited

570+

Published Research Related to This Trial

A systematic review of 15 randomized controlled trials involving newer antiepileptic drugs (AEDs) showed that these medications are significantly more effective than placebo for adults with partial-onset seizures, with a pooled odds ratio of 2.16 for responder rates.

While newer AEDs demonstrated improved efficacy, they also had a higher incidence of adverse effects, indicating a trade-off between effectiveness and safety that needs to be considered in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of the newer antiepileptic drugs as adjunctive treatment in adults with refractory partial-onset epilepsy: a meta-analysis of randomized placebo-controlled trials. Gao, L., Xia, L., Zhao, FL., et al.[2018]

Levetiracetam add-on therapy for 65 children with refractory epilepsy showed a significant response rate of 44.8% after 3 months, increasing to 58.6% after 6 months, indicating its efficacy in reducing seizures.

The therapy had a low adverse reaction rate of only 3%, with symptoms primarily involving dysphoria and behavioral issues, suggesting it is a safe option for managing refractory epilepsy in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical efficacy and safety of levetiracetam add-on therapy for child refractory epilepsy. Chen, J., Liu, XM., Yue, X., et al.[2018]

Levetiracetam (LEV) is a well-tolerated first-line antiseizure medication that shows promising efficacy and minimal drug-drug interactions, making it a valuable option for patients with epilepsy.

The review discusses the development of LEV and its analogs, brivaracetam and padsevonil, which are based on LEV's mechanism of action targeting the synaptic vesicle protein SV2A, highlighting their potential in treating epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil. Wu, PP., Cao, BR., Tian, FY., et al.[2023]

In a study of 72 children and adolescents with epilepsy, lamotrigine (LTG) monotherapy resulted in 42% of patients becoming seizure-free, demonstrating its efficacy in controlling both focal and generalized seizures.

LTG was well-tolerated, with only 6.9% of patients experiencing a rash as an adverse event, and no cases of severe reactions like Stevens-Johnson syndrome, making it a safer option compared to polytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lamotrigine monotherapy in children and adolescents with epilepsy. Valencia, I., Piñol-Ripoll, G., Khurana, DS., et al.[2018]

In a long-term study involving 217 patients with uncontrolled idiopathic generalized epilepsy, adjunctive levetiracetam (LEV) was effective, with 56.2% of patients achieving seizure freedom for at least 6 months across all seizure types.

LEV was generally well tolerated, with 76% of patients reporting at least one mild to moderate treatment-emergent adverse event, and only 7.8% discontinuing due to side effects, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study. Delanty, N., Jones, J., Tonner, F.[2022]

Lamotrigine (LTG) has been confirmed as an effective antiepileptic drug through multiple postmarketing studies, demonstrating its broad applications in managing various epilepsy syndromes.

The most serious side effect associated with LTG is skin rash, and specific guidelines have been established for its concurrent use with valproic acid, especially in pediatric patients, to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lamotrigine. Matsuo, F.[2019]

Lamotrigine (LTG) is recommended as an effective treatment (Level B) for reducing seizure frequency in adults with new-onset focal epilepsy, while levetiracetam (LEV) and zonisamide (ZNS) may also be considered (Level C).

For childhood absence epilepsy, ethosuximide (ETS) or valproic acid (VPA) should be preferred over LTG to decrease seizure frequency, highlighting the importance of selecting appropriate medications based on the type of epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Kanner, AM., Ashman, E., Gloss, D., et al.[2020]

In a 16-week study involving 1541 patients with treatment-resistant partial seizures, levetiracetam (Keppra) was found to be effective as an add-on therapy, with a median seizure frequency reduction of 50.2% and 15.8% of patients becoming seizure-free.

Levetiracetam was generally well tolerated, with 50.5% of patients reporting mild-to-moderate adverse events like somnolence and dizziness, and only 1.0% experiencing serious adverse events, indicating a favorable safety profile for its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SKATE study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy. Steinhoff, BJ., Somerville, ER., Van Paesschen, W., et al.[2018]

In a study of 102 children with refractory epilepsy, levetiracetam (LEV) as add-on therapy led to a reduction in seizure frequency for 45.1% of participants, with 15.6% becoming seizure-free after at least 6 months of treatment.

LEV was particularly effective for children with partial seizures, achieving a 50% reduction in seizure frequency in 58.3% of those patients, and it was generally well-tolerated with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and side effects of levetiracetam on refractory epilepsy in children. Incecik, F., Hergüner, MO., Altunbasak, S.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05364021

NCT05364021 | Study to Investigate LP352 in Subjects ... The objective of this study is to assess the safety, tolerability, efficacy, and pharmacokinetics of adjunctive therapy of LP352 in adults and adolescents

2. lundbeck.com lundbeck.com/us/newsroom/2025/lundbeck-announces-positive-results-from-12-month-open-label-ext

Lundbeck announces positive results from 12-month Open ... Bexicaserin achieved an overall median seizure reduction of 59.3 percent in countable motor seizures over a 12-month open-label extension (OLE) treatment ...

3. aesnet.org aesnet.org/abstractslisting/lp352-a-5-ht2c-superagonist-has-broad-antiepileptic-activity-in-preclinical-seizure-models

lp352, a 5-ht2c superagonist, has broad antiepileptic activity in ... Exp 2: LP352 treatment reduced brain seizure activity an average of 69.1%. ... These data support the potential of LP352 to be useful in ...

4. firstwordpharma.com firstwordpharma.com/story/5814289

Longboard Pharmaceuticals Announces Positive Topline ... Bexicaserin achieved a median seizure reduction of 53.3% in countable motor seizures compared to 20.8% in the placebo group across the DEE ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/epi.18689

Bexicaserin for the treatment of seizures in developmental ... Notably, more than half of the participants receiving bexicaserin experienced ≥50% reductions in frequency of countable motor seizures and total ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05626634

Open-label, Long-term Safety Study of LP352 in Subjects ... The objective of this study is to assess the long-term safety, tolerability, and efficacy of adjunctive therapy of LP352 in subjects with developmental and ...

7. neurology.org neurology.org/doi/10.1212/WNL.98.18_supplement.1771

A Randomized, Double-Blind, Placebo-Controlled, Multiple ... LP352 is a potent and selective 5-HT2c superagonist. LP352 is being developed for the treatment of developmental and epileptic encephalopathies.

8. aesnet.org aesnet.org/abstractslisting/lp352-has-negligible-cyp-or-p-glycoprotein-interaction-potential-minimizing-therapeutic-complexity-in-epilepsy-patients-with-a-high-burden-of-polypharmacy

lp352 has negligible cyp or p-glycoprotein interaction potential ... LP352 was safe and generally well-tolerated, alone or in combination with other probe substrates. Conclusions: Given LP352's disposition via ...