Radiprodil in Participants With Hepatic Impairment

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUClast) of Radiprodil [Срок оценки: 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 [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Maximum Observed Plasma Concentration (Cmax) of Radiprodil [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Time to Maximum Observed Plasma Concentration (Tmax) of Radiprodil [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Time Before First Quantifiable Plasma Concentration (Tlag) of Radiprodil [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Apparent Total Body Clearance (CL/F) of Radiprodil [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) of Radiprodil [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Terminal Elimination Half-Life (t½) of Radiprodil [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]

Вторичные конечные точки (12)

• Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUClast) of FBPO [Срок оценки: 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 [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Maximum Observed Plasma Concentration (Cmax) of FBPO [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Time to Maximum Observed Plasma Concentration (Tmax) of FBPO [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Time Before First Quantifiable Plasma Concentration (Tlag) of FBPO [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Terminal Elimination Half-Life (t½) of FBPO [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Maximum Observed Plasma Concentration (Cmax) of ORR-S [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Time to Maximum Observed Plasma Concentration (Tmax) of ORR-S [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Time Before First Quantifiable Plasma Concentration (Tlag) of ORR-S [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]
• Terminal Elimination Half-Life (t½) of ORR-S [Срок оценки: Day 1 (pre-dose) through Day 6 (120 hours post-dose)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 2 центра

• Epic Medical Research — DeSoto
• Texas Liver Institute — San Antonio

Идентификаторы

NCT: NCT07457229 · RAD-GRIN-505

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗