A Multicenter, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Seizures and Behavioral Symptoms of Radiprodil in Patients with Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) Type II
- Conditions
- Tuberous Sclerosis Complex (TSC), Focal Cortical Dysplasia (FCD) Type IIMedDRA version: 20.0Level: LLTClassification code: 10070672Term: Focal cortical dysplasia Class: 10010331MedDRA version: 21.0Level: PTClassification code: 10080584Term: Tuberous sclerosis complex Class: 100000004850Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- CTIS2023-506301-20-00
- Lead Sponsor
- Grin Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 34
Age range: = 6 months up to 18 years at Part A Baseline, Failed to respond to at least 2 anti-seizure medications (ASMs) at appropriate dosages and durations, Disease specific criteria: a. diagnosis of FCD Type II based on clinical symptoms and confirmed by a positive magnetic resonance imaging (MRI) b. diagnosis of TSC by either clinical or genetic diagnostic criteria (Northrup, 2021) as documented in the participant’s medical record., Participant on average has had at least 8 countable/witnessed primary seizures during a 4 week baseline period with at least 1 seizure occurring in at least 3 of the 4 weeks of Baseline, All medical interventions for epilepsy / behavior (including ketogenic diet and any neurostimulation devices) should be stable for 28 days prior to Screening with no more than 6 days per month use of rescue medication. Participants must remain on a stable regimen throughout the treatment period., Participant’s or their caregivers have signed informed consent and participant has signed assent (if applicable)., Participant’s or their caregivers are willing and able to complete entries in the eDiary on a daily basis., Participant has had an MRI scan within 12 weeks of Screening or during the Screening Period., Participant is 1 of the following: a. Not of childbearing potential (premenarchal or male/not in possession of a uterus). b. If of childbearing potential, is nonpregnant (negative serum pregnancy test results at Screening and negative urine pregnancy test results at Baseline), nonlactating, and practicing 1 of the following medically acceptable methods of birth control: ? Abstinence as a lifestyle choice. ? Hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the participant’s usual menstrual cycle period) before IP administration. ? Intrauterine device. If male, is willing to use a highly effective method of contraception throughout the study period.
Participant with 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., Participant with any clinically significant laboratory or ECG abnormalities that according to the Investigator in consultation with the Sponsor would jeopardize the safety of the participant, limit participation, or compromise the interpretation of the safety data from the participant., Participant has severe hepatic dysfunction (Child-Pugh grade C)., Participant has a history of brain surgery within 6 months of randomization for epilepsy or any other reason., Participant with any contraindications to radiprodil or with known hypersensitivity to the active substance or the excipients or other chemically closely related substances., Participant receiving treatment with contraindicated concomitant drugs such as agonists or antagonists of the glutamate receptor, including but not limited to felbamate, memantine, and perampanel., Participant has received an investigational treatment within 3 months or 5 half-lives of Screening, whichever is longer.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: -To determine the safety and tolerability of multiple individually titrated doses of radiprodil in TSC and FCD Type II patients<br>-To determine the pharmacokinetics (PK) and plasma exposure of radiprodil;Secondary Objective: -To evaluate initial signs of efficacy on frequency and severity of epileptic seizures in those participants with seizures, To evaluate initial signs of efficacy of radiprodil on additional central nervous system (CNS) features including behavior and quality of life;Primary end point(s): Adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) (frequency, type, severity, and duration) over the course of treatment (Part A and Part B) ? Changes in vital signs ? Physical examination findings ? 12-lead electrocardiogram (ECG) findings ? Clinically significant changes in laboratory parameters ? Occurrence of suicidal ideation or behavior Plasma concentrations of radiprodil at predefined timepoints
- Secondary Outcome Measures
Name Time Method