Radiprodil in Participants With Hepatic Impairment

Phase 1, Open-Label Study to Assess the Pharmacokinetics, Safety, and Tolerability of Radiprodil in Hepatically Impaired Participants

This Phase 1, open-label study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of radiprodil in adults with varying degrees of hepatic impairment compared with healthy participants. Radiprodil is being developed as a potential treatment for GRIN-related neurodevelopmental disorders, tuberous sclerosis complex, and focal cortical dysplasia.

Approximately 40 adults aged 18 to 75 years will be enrolled into five cohorts based on liver function (mild, moderate, or severe hepatic impairment) or healthy status. Participants will receive a single 15 mg oral dose of radiprodil and remain in the clinical research unit for intensive PK and safety monitoring through Day 6.

The primary objective is to characterize the PK profile of radiprodil in participants with hepatic impairment compared with healthy participants. Safety and tolerability will also be assessed. Results from this study will help determine whether dose adjustments are needed in individuals with impaired liver function.

Study Overview

• Status: Recruiting
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Radiprodil

Detailed Description

This is a Phase 1, open-label, two-arm study designed to assess the pharmacokinetics (PK), safety, and tolerability of a single oral dose of radiprodil in adults with varying degrees of hepatic impairment compared with matched healthy participants.

Up to 40 participants aged 18 to 75 years will be enrolled across five cohorts. Participants will include individuals with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe (Child-Pugh Class C) hepatic impairment, as well as healthy participants matched for age, sex, and body mass index where feasible.

The study consists of a Screening Period (Days -28 to -2), check-in on Day -1, and a Treatment Period. Participants will be confined to the clinical research unit from Day -1 through completion of study assessments on Day 6. On Day 1, all participants will receive a single oral dose of radiprodil 15 mg administered as an oral suspension.

Serial blood samples will be collected to determine plasma concentrations of radiprodil and its major metabolites. Key PK parameters include area under the concentration-time curve (AUC), maximum observed concentration (Cmax), time to maximum concentration (Tmax), terminal half-life (t½), apparent clearance (CL/F), and apparent volume of distribution (Vz/F).

Safety and tolerability will be evaluated throughout the study by monitoring adverse events, vital signs, electrocardiograms, clinical laboratory tests, physical examinations, and Columbia Suicide Severity Rating Scale assessments.

Hepatic impairment can alter the metabolism and exposure of many drugs. Because radiprodil is primarily eliminated via hepatic metabolism, this study is intended to characterize the effect of liver impairment on radiprodil exposure and to inform potential dosing recommendations for future clinical use.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Laura Bardell; Phone Number: +1-877-225-0014; Email: ClinicalTrials@GrinTherapeutics.com
• Study Contact Backup: Name: Aneeta Saxena

Study Locations

• United States
  • Texas
    • DeSoto, Texas, United States, 75115
      • Recruiting
      • EPIC Medical Research
      • Contact: Haresh Boghara, MD
      • Contact: Ketul Shah, CRC; Phone Number: 979-344-1980; Email: kshah@epicmedresearch.com
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • Texas Liver Institute
      • Contact: Bryan Bernal, CRC; Phone Number: (210) 572-4986; Email: bbernal@txliver.com
      • Contact: Eric Lawtiz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female participants aged 18 to 75 years, inclusive, at Screening.
• Body mass index (BMI) within the range specified in the protocol.
• Participants with hepatic impairment must have stable mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe (Child-Pugh Class C) hepatic impairment, as applicable to cohort assignment.
• Healthy participants must be medically healthy with no clinically significant abnormalities as determined by the investigator.
• Participants must be willing and able to comply with all study procedures and confinement requirements.
• Participants of childbearing potential must agree to use highly effective contraception methods as defined in the protocol.
• Participants must provide written informed consent prior to any study procedures

Exclusion Criteria:

• History or presence of clinically significant medical conditions that could interfere with study participation or interpretation of results.
• Positive test for drugs of abuse, alcohol, or cotinine (where applicable) at Screening or check-in.
• Positive serology for HIV, hepatitis B surface antigen, or hepatitis C virus.
• Clinically significant abnormal laboratory values, vital signs, or ECG findings at Screening or Day -1, as judged by the investigator.
• Use of prohibited concomitant medications or substances that may interfere with radiprodil metabolism.
• Pregnant or breastfeeding women.
• Participation in another clinical study or receipt of an investigational product within the protocol-specified timeframe prior to dosing.
• Any condition that, in the opinion of the investigator or sponsor, would make participation not in the best interest of the participant or could confound study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Hepatic Impairment; Participants with mild hepatic impairment (Child-Pugh Class A).	Drug: Radiprodil; Radiprodil will be administered as a single oral dose of 15 mg (2.0 mL of 7.5 mg/mL oral suspension) on Day 1 under fed conditions. Participants will fast overnight for at least 10 hours prior to dosing and consume a standard breakfast approximately 30 minutes before administration. Study drug will be administered with approximately 240 mL of water. All participants across cohorts will receive the same single-dose regimen.; Other Names: RGH-896; Radiprodil oral suspension
Experimental: Moderate Hepatic Impairment; Participants with moderate hepatic impairment (Child-Pugh Class B).	Drug: Radiprodil; Radiprodil will be administered as a single oral dose of 15 mg (2.0 mL of 7.5 mg/mL oral suspension) on Day 1 under fed conditions. Participants will fast overnight for at least 10 hours prior to dosing and consume a standard breakfast approximately 30 minutes before administration. Study drug will be administered with approximately 240 mL of water. All participants across cohorts will receive the same single-dose regimen.; Other Names: RGH-896; Radiprodil oral suspension
Experimental: Healthy Participants (Matched to Mild/Moderate); Healthy participants matched to the mild and moderate hepatic impairment cohorts by age, sex, and body mass index where feasible.	Drug: Radiprodil; Radiprodil will be administered as a single oral dose of 15 mg (2.0 mL of 7.5 mg/mL oral suspension) on Day 1 under fed conditions. Participants will fast overnight for at least 10 hours prior to dosing and consume a standard breakfast approximately 30 minutes before administration. Study drug will be administered with approximately 240 mL of water. All participants across cohorts will receive the same single-dose regimen.; Other Names: RGH-896; Radiprodil oral suspension
Experimental: Severe Hepatic Impairment; Participants with severe hepatic impairment (Child-Pugh Class C).	Drug: Radiprodil; Radiprodil will be administered as a single oral dose of 15 mg (2.0 mL of 7.5 mg/mL oral suspension) on Day 1 under fed conditions. Participants will fast overnight for at least 10 hours prior to dosing and consume a standard breakfast approximately 30 minutes before administration. Study drug will be administered with approximately 240 mL of water. All participants across cohorts will receive the same single-dose regimen.; Other Names: RGH-896; Radiprodil oral suspension
Experimental: Healthy Participants (Matched to Severe); Healthy participants matched to the severe hepatic impairment cohort by age, sex, and body mass index where feasible.	Drug: Radiprodil; Radiprodil will be administered as a single oral dose of 15 mg (2.0 mL of 7.5 mg/mL oral suspension) on Day 1 under fed conditions. Participants will fast overnight for at least 10 hours prior to dosing and consume a standard breakfast approximately 30 minutes before administration. Study drug will be administered with approximately 240 mL of water. All participants across cohorts will receive the same single-dose regimen.; Other Names: RGH-896; Radiprodil oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUClast) of Radiprodil	Plasma AUClast of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUCinf) of Radiprodil	Plasma AUCinf of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) of Radiprodil	Plasma Cmax of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Time to Maximum Observed Plasma Concentration (Tmax) of Radiprodil	Plasma Tmax of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Time Before First Quantifiable Plasma Concentration (Tlag) of Radiprodil	Plasma Tlag of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Apparent Total Body Clearance (CL/F) of Radiprodil	Apparent total body clearance of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) of Radiprodil	Apparent volume of distribution of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Terminal Elimination Half-Life (t½) of Radiprodil	Plasma terminal elimination half-life of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUClast) of FBPO	Plasma AUClast of the radiprodil major metabolite FBPO following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUCinf) of FBPO	Plasma AUCinf of FBPO following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) of FBPO	Plasma Cmax of FBPO following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Time to Maximum Observed Plasma Concentration (Tmax) of FBPO	Plasma Tmax of FBPO following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Time Before First Quantifiable Plasma Concentration (Tlag) of FBPO	Plasma Tlag of FBPO following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Terminal Elimination Half-Life (t½) of FBPO	Plasma terminal half-life of FBPO following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUClast) of ORR-S	Plasma AUClast of the radiprodil major metabolite ORR-S following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUCinf) of ORR-S	Plasma AUCinf of ORR-S following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) of ORR-S	Plasma Cmax of ORR-S following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Time to Maximum Observed Plasma Concentration (Tmax) of ORR-S	Plasma Tmax of ORR-S following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Time Before First Quantifiable Plasma Concentration (Tlag) of ORR-S	Plasma Tlag of ORR-S following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Terminal Elimination Half-Life (t½) of ORR-S	Plasma terminal half-life of ORR-S following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.	Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Incidence of treatment-emergent adverse events following a single oral dose of radiprodil, summarized by system organ class and preferred term.	Day 1 through Day 6 (120 hours post-dose)
Number of Participants With Serious Adverse Events (SAEs)	Incidence of serious adverse events following a single oral dose of radiprodil.	Day 1 through Day 6 (120 hours post-dose)
Number of Participants With Adverse Events Leading to Discontinuation	Incidence of participants who discontinue the study due to an adverse event following a single oral dose of radiprodil.	Day 1 through Day 6 (120 hours post-dose)
Change From Baseline in Systolic Blood Pressure (mmHg)	Change from baseline in systolic blood pressure following a single oral dose of radiprodil.	Baseline (Day -1) through Day 6 (120 hours post-dose)
Change From Baseline in Diastolic Blood Pressure (mmHg)	Change from baseline in diastolic blood pressure following a single oral dose of radiprodil.	Baseline (Day -1) through Day 6 (120 hours post-dose)
Change From Baseline in Heart Rate (beats per minute)	Change from baseline in heart rate following a single oral dose of radiprodil.	Baseline (Day -1) through Day 6 (120 hours post-dose)
Change From Baseline in Respiratory Rate (breaths per minute)	Change from baseline in respiratory rate following a single oral dose of radiprodil.	Baseline (Day -1) through Day 6 (120 hours post-dose)
Change From Baseline in Body Temperature (°C)	Change from baseline in body temperature following a single oral dose of radiprodil.	Baseline (Day -1) through Day 6 (120 hours post-dose)
Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) (milliseconds)	Change from baseline in QT interval corrected using Fridericia's formula (QTcF) following a single oral dose of radiprodil.	Baseline (Day -1) through Day 6 (120 hours post-dose)
Number of Participants With Clinically Significant Laboratory Abnormalities	Incidence of participants with laboratory values meeting predefined criteria for clinical significance across hematology, serum chemistry, coagulation, and urinalysis following a single oral dose of radiprodil.	Baseline (Day -1) through Day 6 (120 hours post-dose)
Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score	Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) score following a single oral dose of radiprodil.	Baseline (Day -1) through Day 6 (120 hours post-dose)

Collaborators and Investigators

• Sponsor: GRIN Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hepatic impairment; Radiprodil
• Additional Relevant MeSH Terms: radiprodil
• Other Study ID Numbers: RAD-GRIN-505

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No