A Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms of Multiple Individually Titrated Doses of Radiprodil in Children with GRIN-related Disorder.

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 4

Inclusion Criteria

For Part A and Part B (unless stated otherwise):
1. For Part A, pediatric participants aged >=6 months to <=12 years with GRIN 1,
2A, 2B, or 2D gene variants known to result in GoF of the NMDA receptor. For
Part B, pediatric participants aged >=6 months with GRIN 1, 2A, 2B, or 2D gene
variants known to result in GoF of the NMDA receptor.
2. Participant to be enrolled in the first cohort experiences the following
(Part A only):
a) At least 1 observable motor seizure per week and >=4 observable motor
seizures (generalized or focal) during the prospective 4-week Observation
Period.
b) Has failed to obtain adequate seizure control with at least 2 ASMs used at
appropriate dose and duration with assured medication adherence (if applicable).
3. Participant to be enrolled in the second cohort experiences the following
(Part A only):
a) Significant behavioral and/or motor symptoms based on caregiver report with
a CGI-S score >=4 at the Screening Visit and Day -1 of Visit T1.
4. For part A, current therapies need to be on a stable dose for at least 4
weeks prior to Screening and should be maintained stable throughout the whole
study duration, nonpharmacological treatments such as ketogenic diet should be
kept as stable as possible during screening and participation in the study.
Changes in antiseizure medication should be discussed with the sponsor in
consultation with the investigator.
For all inclusion criteria see Protocol.
Rescreening criteria for Part B only:
1. Participant has received at least 8 weeks of treatment (combined Titration
and Maintenance Period) with radiprodil during Part A.
2. The benefit-risk of continuing radiprodil treatment remains favorable as
determined by the investigator*s clinical assessment and is eligible to
continue treatment according to the judgement of the investigator.

Exclusion Criteria

Exclusion criteria (at initial Screening and following completion of the
Maintenance Period of Part A, unless stated otherwise): 1. Participant with any
other clinically relevant medical, neurologic, or psychiatric condition and/or
behavioral disorder unrelated to GRIN related disorders 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. 2.
Participant with a body weight <10 kg on Day -1 of Visit T1 for whom a gastric
tube is the only possibility for radiprodil dosing (during treatment with the
first dose in Part A only). 3. Participant with any clinically significant
laboratory or ECG abnormalities. 4. Participant has severe hepatic dysfunction
(Child-Pugh grade C). 5. Participant has a history of brain surgery for
epilepsy or any other reason. For all exclusion criteria see Protocol.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• Adverse events (AEs), serious adverse events (SAEs), and adverse drug<br /><br>reactions (ADRs) (frequency, type, severity, and duration)<br /><br>• Changes in vital signs<br /><br>• Physical examination findings<br /><br>• 12-lead electrocardiogram (ECG) findings<br /><br>• Clinically significant changes in laboratory parameters<br /><br>• Emergence of new seizure types<br /><br>• Occurrence of suicidal ideation or behavior<br /><br><br /><br>• Determination of the maximum tolerated dose of radiprodil based on safety and<br /><br>tolerability data<br /><br><br /><br>• Plasma concentrations of radiprodil at predefined timepoints</p><br>

Secondary Outcome Measures

Name	Time	Method

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