Radiprodil in Participants With Hepatic Impairment

Purpose

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.

Condition

  • Hepatic Impairment

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Participants will be assigned to parallel cohorts based on hepatic function (mild, moderate, or severe hepatic impairment) or healthy status. All participants will receive a single oral dose of radiprodil 15 mg. Healthy participants will be enrolled to match hepatically impaired cohorts by age, sex, and body mass index where feasible. Cohorts will be initiated sequentially following Safety Review Committee review of available safety and pharmacokinetic data, but participants will not cross over between cohorts.
Primary Purpose
Other
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Epic Medical Research
DeSoto, Texas 75115
Contact:
Ketul Shah, CRC
979-344-1980
kshah@epicmedresearch.com

Texas Liver Institute
San Antonio, Texas 78215
Contact:
Bryan Bernal, CRC
(210) 572-4986
bbernal@txliver.com

More Details

Status
Recruiting
Sponsor
GRIN Therapeutics, Inc.

Study Contact

Laura Bardell
+1-877-225-0014
ClinicalTrials@GrinTherapeutics.com

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.