Overview
Study RAD-GRIN-201 is a phase 1B/2A trial to assess safety, tolerability, pharmacokinetics (PK), and potential efficacy of radiprodil in participants with Tuberous Sclerosis Complex (TSC) or Focal Cortical Dysplasia (FCD) type II. The study is open-label, so all participants will be treated with radiprodil. Subjects' participation in the study is expected to last up to six months in Part A and one year in Part B/long-term treatment period. The treatment period in Part B may be extended based on a favorable benefit/risk profile.
Description
Approximately 20 participants with TSC and 10 participants with FCD type II will be enrolled.
The effects of radiprodil are assessed in participants with treatment-resistant seizures (with or without behavioral symptoms). The daily doses of radiprodil will be individually titrated for every participant and all the participants will receive study drug.
This study is divided into the following periods:
PART A:
- Screening/Observation Period (up to six(6) weeks): Investigators assess eligibility followed by an Observation Period (at least four(4) weeks) to evaluate seizure frequency.
- Titration Period (approx. four(4) weeks): Radiprodil twice daily will be administered in escalating doses and plasma concentrations, safety, and tolerability assessed. Once a safe and potentially effective dose has been established, the participant will immediately enter the Maintenance Period.
- Maintenance Period (approx. twelve(12) weeks): The participant will continue to take the safe and potentially effective dose identified during the Titration Period. At the end of the Maintenance Period the participant will either be invited to enter Part B or the Tapering and Safety Follow-up Period.
- Tapering (15 days) and Safety Follow-up Period (14 days): a participant who doesn't take part in the long-term treatment period (Part B) will taper (ie gradually decrease) the study medicine for 15 days and enter a safety Follow-up Period (14 days). In this case, the participant will have one (1) last visit at the end of the safety Follow-up Period.
PART B:
- Long-Term Treatment Period (one(1) year): During the Long-Term Treatment Period (Part B), participants will continue taking radiprodil at the usual dose level and making regular visits to the study site.
- Tapering (15 days) and Safety Follow-up Period (14 days): at the end of the long-term treatment period (Part B), the participant will taper (ie gradually decrease) the study medicine for 15 days and enter a safety Follow-up Period (14 days) after his/her last dose of radiprodil. The participant will have one (1) last visit at the end of the safety Follow-up Period.
Eligibility
Inclusion Criteria:
- Failed to respond to at least 2 anti-seizure medications (ASMs) at appropriate dosages and duration.
- Disease specific criteria:
- diagnosis of FCD Type II based on clinical symptoms and confirmed by a positive magnetic resonance imaging (MRI)
- diagnosis of TSC by either clinical or genetic diagnostic criteria (Northrup,
- 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 has had an MRI scan within 12 months of the planned date of first dose of study drug.
Exclusion Criteria:
- 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.
- Severe hepatic dysfunction (Child-Pugh grade C).
- History of brain surgery within 6 months of screening for epilepsy or any other reason.
- Contraindications to radiprodil or with known hypersensitivity to the active substance or the excipients or other chemically closely related substances.
- Receiving treatment with contraindicated concomitant drugs such as agonists or antagonists of the glutamate receptor, including but not limited to felbamate, memantine, and perampanel.
- body weight <10kg for whom a gastric tube is the only possibility for radiprodil dosing.
