Radiprodil for Seizures

Recruiting at 23 trial locations

Overseen By Clinical Operations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: GRIN Therapeutics, Inc.

Must be taking: Anti-seizure medications

Must not be taking: Glutamate receptor drugs

Disqualifiers: Severe hepatic dysfunction, Brain surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new medication, radiprodil, for individuals with Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) type II, both of which can cause frequent seizures. The study is open-label, so all participants will receive the treatment. Those who have tried at least two anti-seizure medications without success and experience frequent seizures may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new medication.

Will I have to stop taking my current medications?

The trial requires that participants stay on their current stable medication regimen for epilepsy and behavior throughout the treatment period.

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

Research has shown that radiprodil is usually well-tolerated by patients. Safety information from earlier studies with over 400 participants suggests it rarely causes serious side effects. These studies also indicate that radiprodil may help reduce seizures and is being tested for use in conditions like Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) type II. Although more research is needed for confirmation, the current data is encouraging for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for seizures?

Radiprodil is unique because it targets NMDA receptors in the brain, which are involved in the transmission of signals that can lead to seizures. Unlike other treatments for seizures, which often focus on general suppression of neuronal activity, radiprodil offers a more targeted approach, potentially leading to fewer side effects. Researchers are excited about this treatment because it could offer a new option for patients who don't respond well to current anti-seizure medications, giving hope for better management of their condition.

What evidence suggests that radiprodil might be an effective treatment for seizures in TSC or FCD type II?

Research has shown that radiprodil may help reduce seizures. In earlier studies, people treated with radiprodil experienced 86% fewer countable motor seizures, a specific type of seizure, compared to before treatment. The drug targets a part of the brain involved in excessive signaling that can lead to seizures. This trial tests radiprodil's effectiveness in conditions like Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) type II, which involve seizures. Initial results are promising, but more research is needed to confirm these findings for these specific conditions. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia type II who experience seizures and behavioral symptoms. Participants will be involved in the study for up to six months initially, with a possible extension to one year if benefits outweigh risks.

Inclusion Criteria

My epilepsy treatment has been stable for the last 28 days with limited emergency medication use.

I have been diagnosed with FCD Type II confirmed by an MRI.

I have been diagnosed with TSC either through symptoms or genetic testing.

Exclusion Criteria

I had brain surgery within the last 6 months.

Any other clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder unrelated to TSC or FCD Type II that would preclude or jeopardize participant's safe participation or administration of study drug or the conduct of the study according to the judgement of the investigator

Clinically significant laboratory or ECG abnormalities

Timeline for a Trial Participant

Screening/Observation

Participants are screened for eligibility to participate in the trial followed by an Observation Period to evaluate seizure frequency

6 weeks

Titration

Radiprodil is administered in escalating doses to assess plasma concentrations, safety, and tolerability

4 weeks

Maintenance

Participants continue taking the safe and potentially effective dose identified during the Titration Period

12 weeks

Tapering and Safety Follow-up

Participants taper off the study medication and enter a safety follow-up period

4 weeks

Long-Term Treatment

Participants continue taking radiprodil at the usual dose level with regular visits to the study site

1 year

Tapering and Safety Follow-up

Participants taper off the study medication and enter a safety follow-up period after the long-term treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Radiprodil

Trial Overview The trial is testing Radiprodil's safety, how well it's tolerated by patients, its behavior in the body (pharmacokinetics), and its effectiveness on reducing seizures and improving behavioral symptoms in participants.

How Is the Trial Designed?

Group I: TSC Experimental Treatment 1 Intervention

Liquid suspension of radiprodil, at concentrations 0.25 mg/mL or 2.50 mg/mL for 1% and 10% formulation respectively. It will be administered twice a day (bid) either orally or via gastric or nasogastric tube.

Group II: FCD Type II Experimental Treatment 1 Intervention

Liquid suspension of radiprodil, at concentrations 0.25 mg/mL or 2.50 mg/mL for 1% and 10% formulation respectively. It will be administered twice a day (bid) either orally or via gastric or nasogastric tube.

Who Is Running the Clinical Trial?

GRIN Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

In a study using rabbits, the D-1 antagonist SCH 23390 significantly decreased the susceptibility to seizures, while the D-2 antagonist haloperidol increased seizure susceptibility, indicating a marked difference in their effects on epilepsy.

The findings suggest that D-1 and D-2 dopamine receptor subtypes play distinct roles in the mechanisms of seizures, which could inform future treatments for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of the dopaminergic system in experimental models of epilepsy]. Bo, P., Soragna, D., Murelli, R., et al.[2013]

Dopamine D1 receptor agonists, like SKF 38393, can induce seizures in mice previously treated with reserpine, but this effect can be blocked by D2 receptor agonists or D1 receptor antagonists, indicating a complex interaction between these receptors in seizure modulation.

In rats, the D2 agonist LY 171555 showed anticonvulsant properties against pilocarpine-induced seizures, suggesting that targeting D2 receptors may provide a therapeutic approach to manage seizures, while D1 receptor activation appears to increase seizure susceptibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opposite effects of stimulation of D1 and D2 dopamine receptors on the expression of motor seizures in mouse and rat. al-Tajir, G., Chandler, CJ., Starr, BS., et al.[2019]

Dopamine D1 receptor agonists, particularly SKF 38393, showed a dose-dependent ability to block seizures induced by pentylenetetrazole, indicating their potential as anticonvulsants.

The D1/D2 agonist apomorphine also effectively blocked seizures, suggesting that its anticonvulsant effects are linked to the activation of both D1 and D2 receptors, potentially enhancing GABA transmission in specific brain regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dopamine D1 and D2 receptor agonists and antagonists on seizures induced by chemoconvulsants in mice. Ogren, SO., Pakh, B.[2019]

D3 receptor agonists, particularly RU 24213, can significantly delay the onset of limbic motor seizures induced by pilocarpine in rats, indicating a potential anticonvulsant effect, especially at low doses.

The study suggests that the protective effects against seizures are more likely mediated by D2 receptors rather than D3 receptors, as other selective D3 agonists did not provide the same level of protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dopamine D3 receptor agonists on pilocarpine-induced limbic seizures in the rat. Alam, AM., Starr, MS.[2019]

Bromocryptine significantly reduces both total and lethal audiogenic seizures in 21-day-old DBA/2H mice, with the protective effect increasing within the first hour after administration.

The protective effect of bromocryptine is blocked by spiroperidol, indicating that dopaminergic pathways play a crucial role in inhibiting audiogenic seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of audiogenic seizures by bromocryptine. González Pérez, JN., González-Quevedo, A.[2019]

Citations

1. practicalneurology.com practicalneurology.com/news/radiprodil-designated-a-breakthrough-therapy-for-grin-related-neurodevelopmental-disorder/2473793/

Radiprodil Designated a Breakthrough Therapy for GRIN ... Treatment with radiprodil was associated with an 86% reduction from baseline in countable motor seizures (CMS). 71% of radiprodil-treated ...

2. clinicaltrials.eu clinicaltrials.eu/inn/radiprodil/

Radiprodil: A Promising New Drug for Neurological Disorders These trials aim to evaluate the safety, effectiveness, and proper dosing of radiprodil in treating seizures and behavioral symptoms associated with these ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38529699/

Radiprodil, a selective GluN2B negative allosteric ... Our data clearly show that radiprodil, a GluN2B selective negative allosteric modulator, may have the potential to control seizures in patients with GRIN2A GoF ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05818943

NCT05818943 | Honeycomb: Evaluation of Radiprodil in ... The effect of radiprodil is assessed in two (2) cohorts of pediatric participants: one (1) cohort of participants with treatment-resistant seizures (with or ...

5. curegrin.org curegrin.org/radiprodil-reduces-seizures-in-grin-gain-of-function-patients-by-a-median-of-86-in-first-ever-commercial-clinical-trial-for-gri-disorders/

Radiprodil reduces seizures in GRIN (gain-of-function) ... Radiprodil reduced seizures among people with gain-of-function GRIN Disorders by a median of 86% in a Phase 1B clinical trial, according to GRIN Therapeutics.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06392009

Astroscape: A Study of Radiprodil on Safety, Tolerability, ... Astroscape: A Study of Radiprodil on Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms in Patients With TSC or FCD Type II.

7. aesnet.org aesnet.org/abstractslisting/pharmacokinetics-safety-tolerability-and-effect-on-seizure-frequency-and-behavior-of-individually-titrated-radiprodil-doses-in-children-with-grin-related-disorder-top-line-multicenter-study-data

Abstracts - American Epilepsy Society Radiprodil appears to be well-tolerated to date with potential signs of meaningful clinical effects in this severe disorder with high unmet need.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6349788/

A pharmacokinetic study of radiprodil oral suspension in ... Safety and tolerability. The secondary objectives of this study were to evaluate the safety and tolerability of radiprodil oral suspension. During the study ...

9. bioworld.com bioworld.com/articles/720485-grins-radiprodil-heads-to-phase-iii-with-570m-deal-140m-series-d

Grin's radiprodil heads to phase III with $570M deal, $140 ... “That study failed, [but it] did deliver north of 400 patients of safety data, which was helpful to us,” Leuchter said. At some point ...