RAP-219 for Partial Seizures

Recruiting at 14 trial locations

Overseen By Beth Bowers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rapport Therapeutics Inc.

Disqualifiers: Generalized seizures, Status epilepticus, Epilepsy surgery, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial allows participants to continue taking up to 4 antiseizure medications, so you may not need to stop your current medications if they fit within this limit.

What data supports the effectiveness of the drug RAP-219 for partial seizures?

The research shows that lacosamide, a component of RAP-219, is effective as an additional treatment for adults with partial seizures, as it has been tested in several studies and found to be safe and effective. ^{1 2 3 4 5}

What safety data exists for RAP-219 in humans?

Lacosamide, which may be related to RAP-219, has been studied for safety in treating partial-onset seizures. In clinical trials, it was generally well-tolerated, but some people experienced side effects like dizziness and sleepiness. Long-term studies also support its safety when used alone for these seizures. ^{1 6 7 8 9}

What is the purpose of this trial?

This is a clinical research study for an investigational drug called RAP-219 in patients with Refractory Focal Epilepsy. This study is being conducted to determine if RAP-219 works and is safe in patients with Refractory Focal Epilepsy.

Research Team

Jaqueline A French, MD

Principal Investigator

NYU Langone Comprehensive Epilepsy Center

Eligibility Criteria

This trial is for adults with Refractory Focal Epilepsy who have not responded well to other treatments. Participants can be on up to four seizure medications and must have an implanted neurostimulator device that meets specific criteria. They should have had at least one seizure in the past 8 weeks, be in good health overall, and able to follow the study's procedures.

Inclusion Criteria

I am taking no more than 4 medications for seizures.

I have had at least one seizure in the last 8 weeks.

Willing and able to adhere to all aspects of the protocol

Exclusion Criteria

Individuals of reproductive potential who do not agree to simultaneously use two effective birth-control methods

I had epilepsy surgery within the last year.

I have had seizures that affect both sides of my brain in the last 10 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 0.75 mg RAP-219 daily for 5 days followed by 1.25 mg RAP-219 daily for the remainder of the 8-week treatment period

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 months

Treatment Details

Interventions

• RAP-219

Trial Overview The trial is testing RAP-219, a new drug for people with difficult-to-treat seizures. The goal is to see if it's effective and safe when used alongside current epilepsy treatments.

Participant Groups

Group I: RAP-219 Experimental Treatment 1 Intervention

Participants will receive 0.75 mg RAP-219 daily for 5 days followed by 1.25 mg RAP-219 daily for the remainder of the 8-week treatment period.

Who Is Running the Clinical Trial?

Rapport Therapeutics Inc.

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

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]

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]

In a study involving 313 adults with refractory partial seizures, rufinamide at 1600 mg twice daily led to a significant 20.4% median reduction in seizure frequency compared to a 1.6% increase in the placebo group, indicating its efficacy as an adjunctive treatment.

Rufinamide was generally well tolerated, with common side effects including dizziness and nausea, primarily occurring during the initial titration phase, suggesting it is a safe option for patients when monitored appropriately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial. Brodie, MJ., Rosenfeld, WE., Vazquez, B., et al.[2019]

A systematic review of 70 randomized trials involving over 14,000 patients found that new antiepileptic drugs (AEDs) significantly improve seizure control compared to placebo, with a responder rate odds ratio of 3.00, indicating a strong efficacy in reducing seizures by at least 50%.

Topiramate was identified as the most effective AED in indirect comparisons, while gabapentin and lacosamide were found to be less effective, highlighting the importance of considering individual patient characteristics and tolerability when choosing AEDs for partial refractory epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical comparability of the new antiepileptic drugs in refractory partial epilepsy: a systematic review and meta-analysis. Costa, J., Fareleira, F., Ascenção, R., et al.[2022]

Perampanel (PER) was found to be significantly more effective than placebo in treating partial onset seizures, showing higher responder rates and seizure freedom in a systematic review of 12 randomized controlled trials involving multiple anti-epileptic drugs.

In terms of safety, PER had the lowest odds of withdrawal due to adverse events compared to other recently approved anti-epileptic drugs, indicating a superior safety profile while still being equally effective as its counterparts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of perampanel and other recently approved anti-epileptic drugs for the treatment of refractory partial onset seizure: a systematic review and Bayesian network meta-analysis. Khan, N., Shah, D., Tongbram, V., et al.[2021]

In a study of 1,807,347 first-time users of desloratadine (DL) in Nordic countries, there was a 46% increased incidence of seizures during periods of DL exposure compared to unexposed periods, particularly in children aged 0-5 years.

The adjusted incidence rate ratio for seizures was significantly higher in young children (1.85) but showed no increased risk in adults aged 20 years or older, indicating that younger populations may be more vulnerable to this potential side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015. Ersbøll, AK., Sengupta, K., Pukkala, E., et al.[2022]

In a study of 122 patients with focal epilepsy treated with perampanel for an average of 20.1 months, 27% achieved seizure freedom for at least 3 months, and 42% experienced a significant reduction in seizure frequency (50-100%).

While adverse events (AEs) were reported in 47% of patients, most notably dizziness and fatigue, these side effects often improved with a dose reduction, indicating that perampanel is generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year real-world experience with perampanel in patients with refractory focal epilepsy: Austrian data. Rohracher, A., Kalss, G., Leitinger, M., et al.[2022]

In a study of 281 patients with partial-onset seizures, adjunctive treatment with perampanel (PER) resulted in a 60% retention rate after six months, with 15% of patients becoming seizure-free in the preceding three months.

While PER can provide significant benefits for difficult-to-treat epilepsy patients, it is associated with a high incidence of adverse events (52%), primarily somnolence and dizziness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter survey of clinical experiences with perampanel in real life in Germany and Austria. Steinhoff, BJ., Hamer, H., Trinka, E., et al.[2021]

In a 2-year open-label extension study involving 322 patients with partial-onset seizures, lacosamide (LCM) demonstrated a favorable long-term safety profile, with 90.7% of patients achieving LCM monotherapy at some point during the study.

The majority of patients experienced significant seizure reduction, with 74.2% achieving a ≥50% reduction in seizures and 5.6% being seizure-free at 24 months, supporting the efficacy of LCM as a long-term monotherapy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial. Vossler, DG., Wechsler, RT., Williams, P., et al.[2018]

References

1. 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]

2. Netherlands 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. [2018]

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

Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial. [2019]

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

Clinical comparability of the new antiepileptic drugs in refractory partial epilepsy: a systematic review and meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of perampanel and other recently approved anti-epileptic drugs for the treatment of refractory partial onset seizure: a systematic review and Bayesian network meta-analysis. [2021]

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

Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Two-year real-world experience with perampanel in patients with refractory focal epilepsy: Austrian data. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A multicenter survey of clinical experiences with perampanel in real life in Germany and Austria. [2021]

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

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial. [2018]