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.
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
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
40
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.
Epic Medical Research
DeSoto, Texas, United States
RECRUITINGTexas Liver Institute
San Antonio, Texas, United States
RECRUITINGArea 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Aneeta Saxena
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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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline (Day -1) through Day 6 (120 hours post-dose)