Phase 1, Open-label, Drug-drug Interaction Study to Assess Effect Between Radiprodil and the Co-administered Drugs.

NCT06975605 | Completed Phase 1

• 1 other identifier: RAD-GRIN-506
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, 3-period study to determine radiprodil's potential to act as a perpetrator of cytochrome P-450 (CYP) metabolic pathways and transporter pathways. The study will evaluate the pharmacokinetics (PK) and safety effects of co-administration of radiprodil with oral midazolam, rosuvastatin, warfarin, digoxin, and omeprazole in healthy adult subjects. The study will be conducted in 1 cohort of healthy adult participants only.

Conditions

Tuberous Sclerosis Complex (TSC); Focal Cortical Dysplasia; Other Neurological Disorders

Keywords

healthy adults; tuberous sclerosis; focal cortical dysplasia

Outcome Measures

Primary Outcomes (10)

• To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of warfarin following repeated oral doses of radiprodil.

  Blood samples will be assessed.

  Day1 - Predose, 0.5 hour,1 hour, 1.5, 2, 3, 4, 8, 12 Day 15 - 24 hours post dose, 48 hour, 96, 120, 144 hours

• To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of warfarin following repeated oral dosing of radiprodil.

  Blood plasma samples will be assessed

  Blood samples for plasma PK will be collected on the following days. - S-warfin - Day1 - Predose, 0.5 hour,1 hour, 1.5, 2, 3, 4, 8, 12 Day 15 - 24 hours post dose, 48 hour, 96, 120, 144 hours

• To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of midazolam following repeated oral doses of radiprodil.

  Blood plasma samples will be assessed

  Day 1 - Pre-dose, 0.5, 1, 1.5, 2, 3, 4 , 8, 12, 24 hour day 15- 24 hour post dose -

• To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of midazolam following repeated oral dosing of radiprodil

  Blood plasma samples will be assessed

  Day 1 - Pre-dose, 0.5, 1, 1.5, 2, 3, 4 , 8, 12, 24 hour day 15- 24 hour post dose -Digoxin- Day 3- predose, 0.5 hour, 1 , 1.5, 2,3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose.

• To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of digoxin following repeated oral doses of radiprodil.

  Blood plasma samples will be assessed

  Day 3- predose, 0.5 hour, 1 , 1.5, 2,3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose

• To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of digoxin following repeated oral dosing of radiprodil.

  Blood plasma samples will be assessed

  Day 3- predose, 0.5 hour, 1 , 1.5, 2,3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose

• To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of rosuvastatin following repeated oral doses of radiprodil.

  Blood plasma samples will be assessed

  Day 3 - pre-dose, 0.5, 1,5, 2, 3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose

• To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of rosuvastatin following repeated oral dosing of radiprodil

  Blood plasma samples will be assessed

  Day 3 - pre-dose, 0.5, 1,5, 2, 3, 4, 8, 12, 24 hour Day 17 - 24 hour post dose

• To assess the effect of oral radiprodil on the plasma PK parameter (AUC) of single oral dose of omeprazole following repeated oral doses of radiprodil.

  Blood plasma samples will be assessed

  Day 5 - pre-dose, 0.5, 1,5, 2, 3, 4, 8, 12, 24 hour Day 19 - 24 hourpost dose

• To assess the effect of oral radiprodil on the plasma PK parameter (CMax) of single oral dosing of omeprazole following repeated oral dosing of radiprodil.

  Blood plasma samples will be assessed

  Day 5 - pre-dose, 0.5, 1,5, 2, 3, 4, 8, 12, 24 hour Day 19 - 24 hourpost dose

Secondary Outcomes (19)

• To assess the safety of oral dosing of radiprodil co-administered with midazolam.

  Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose.

• To assess the safety of oral dosing of radiprodil co-administered with digoxin

  Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose

• To assess the safety of oral dosing of radiprodil co-administered with rosuvastatin.

  Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose

• To assess the safety of oral dosing of radiprodil co-administered with omeprazole

  Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose.

• To assess the safety of oral dosing of radiprodil co-administered with oral warfarin.

  Adverse events: will be assessed throughout the study period from Day -1 untill Day 24 (End of StudyVisit/Early Termination Visit) and Follow up (Telephone call) which is 30 days post last dose.

Study Arms (1)

Experimental Cohort

EXPERIMENTAL

Study Drug - Radiprodil will be administred using a sequential cocktail approach consisting of substrates of multipleCYP enzymes or transporters.

Drug: Radiprodil + co-administered drugs

Interventions

Radiprodil + co-administered drugs DRUG

Study drug radiprodil will be administered asbelow in a sequential manner. \- Radiprodil 7.5 mg, 15 mg and 30 mg will be administered in a sequential manner. Co-administered drugs include: - Warfarin - 10 mg tablets, midazolam 1 mg, digoxin 0.25 mg, rosuvastatin 10 mg, omeprazole 20 mg, Vitamin K - 10 mg.

Experimental Cohort

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (BMI) between 18 and 32 kg/m2 (inclusive) and weighs at least 50 kg at Screening.
• Female participants must be non-lactating and of non-child-bearing potential.
• Male participants if engaging in sexual intercourse with a female partner who could become pregnant must agree to use adequate contraception.
• Participant is of Caucasian origin (note: people of Filipino, Chinese, Japanese, Korean, Vietnamese or Asian-Indian origin are excluded due to higher exposure following rosuvastatin administration).
• Ability to provide signed informed consent and to understand and comply with the requirements of the study including dietary requirements and requirement to stay confined on site for the duration of the study

You may not qualify if:

• History of contraindications or hypersensitivity to radiprodil or any components of the formulations or history of hypersensitivity to warfarin, midazolam, digoxin, rosuvastatin, omeprazole, or vitamin K.
• Female participants who are pregnant, breastfeeding, or have a positive pregnancy test at Screening.
• History or presence of significant (in the opinion of the PI) cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, urologic, neurological, malignancy, psychiatric disease, or brain surgery or injury.
• Any surgical or medical condition that, in the opinion of the PI, could interfere with the absorption, distribution, metabolism, or excretion of the drug.
• History of any CS allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic seasonal allergies at time of dosing on Day 1).
• History of illicit drug abuse or alcohol abuse use within 2 years of Screening.
• History of suicide attempts or deliberate self-harm, or a score of 4 or 5 on ideation or any suicidal behavior on the C-SSRS.
• Routine consumption of more than 2 units of alcoholic beverages per day or more than 14 units per week (a unit of alcohol is equivalent to 1 can of beer, 1 glass of wine, or the equivalent of 1 alcoholic drink).
• Routine consumption of an average of more than five (5) 240 mL servings of coffee or other caffeinated beverages per day.
• A positive test result for amphetamines, barbiturates, benzodiazepines, cocaine, methadone, methamphetamines, opiates, methylenedioxymethamphetamine, phencyclidine, tetrahydrocannabinol, cotinine, or alcohol at Screening or Day -1.
• Use of marijuana (including prescribed marijuana) within 30 days of Day -1.
• Use of tobacco-containing products and nicotine or nicotine containing products in the 2 months prior to Day 1.
• Use of any IP and prescription drug within 30 days of Day -1 or within 5 half-lives whichever is longer.
• Use of any over-the-counter (OTC) medication, including herbal products within the 14 days or 5 half-lives prior to dosing, whichever is longer.
• Any vaccine within 7 days of Day -1.

Sponsors & Collaborators

• GRIN Therapeutics, Inc.: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (1)

Nucleus Network Melbourne

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Tuberous Sclerosis; Focal Cortical Dysplasia

Interventions

radiprodil

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label study
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study drugs will be administered using a sequential cocktail approach consisting of substrates of multipleCYP enzymes or transporters.

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: May 16, 2025
• Study Start: May 20, 2025
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)