Phase 1, Open-Label Study to Assess the Pharmacokinetics, Safety, and Tolerability of Radiprodil in Hepatically Impaired Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUClast) of Radiprodil
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Mild Hepatic Impairment
Participants with mild hepatic impairment (Child-Pugh Class A).
干预措施: Radiprodil (Drug)
Moderate Hepatic Impairment
Participants with moderate hepatic impairment (Child-Pugh Class B).
干预措施: Radiprodil (Drug)
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.
干预措施: Radiprodil (Drug)
Severe Hepatic Impairment
Participants with severe hepatic impairment (Child-Pugh Class C).
干预措施: Radiprodil (Drug)
Healthy Participants (Matched to Severe)
Healthy participants matched to the severe hepatic impairment cohort by age, sex, and body mass index where feasible.
干预措施: Radiprodil (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUClast) of Radiprodil
时间窗: Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Plasma AUClast of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.
Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity (AUCinf) of Radiprodil
时间窗: Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Plasma AUCinf of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.
Maximum Observed Plasma Concentration (Cmax) of Radiprodil
时间窗: Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Plasma Cmax of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.
Time to Maximum Observed Plasma Concentration (Tmax) of Radiprodil
时间窗: Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Plasma Tmax of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.
Time Before First Quantifiable Plasma Concentration (Tlag) of Radiprodil
时间窗: Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Plasma Tlag of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.
Apparent Total Body Clearance (CL/F) of Radiprodil
时间窗: Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Apparent total body clearance of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.
Apparent Volume of Distribution Based on the Terminal Phase (Vz/F) of Radiprodil
时间窗: Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Apparent volume of distribution of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.
Terminal Elimination Half-Life (t½) of Radiprodil
时间窗: Day 1 (pre-dose) through Day 6 (120 hours post-dose)
Plasma terminal elimination half-life of radiprodil following a single oral dose in participants with varying degrees of hepatic impairment and healthy participants.
次要结局
- Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUClast) of FBPO(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(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Maximum Observed Plasma Concentration (Cmax) of FBPO(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Time to Maximum Observed Plasma Concentration (Tmax) of FBPO(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Time Before First Quantifiable Plasma Concentration (Tlag) of FBPO(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Terminal Elimination Half-Life (t½) of FBPO(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(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(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Maximum Observed Plasma Concentration (Cmax) of ORR-S(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Time to Maximum Observed Plasma Concentration (Tmax) of ORR-S(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Time Before First Quantifiable Plasma Concentration (Tlag) of ORR-S(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Terminal Elimination Half-Life (t½) of ORR-S(Day 1 (pre-dose) through Day 6 (120 hours post-dose))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Day 1 through Day 6 (120 hours post-dose))
- Number of Participants With Serious Adverse Events (SAEs)(Day 1 through Day 6 (120 hours post-dose))
- Number of Participants With Adverse Events Leading to Discontinuation(Day 1 through Day 6 (120 hours post-dose))
- Change From Baseline in Systolic Blood Pressure (mmHg)(Baseline (Day -1) through Day 6 (120 hours post-dose))
- Change From Baseline in Diastolic Blood Pressure (mmHg)(Baseline (Day -1) through Day 6 (120 hours post-dose))
- Change From Baseline in Heart Rate (beats per minute)(Baseline (Day -1) through Day 6 (120 hours post-dose))
- Change From Baseline in Respiratory Rate (breaths per minute)(Baseline (Day -1) through Day 6 (120 hours post-dose))
- Change From Baseline in Body Temperature (°C)(Baseline (Day -1) through Day 6 (120 hours post-dose))
- Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) (milliseconds)(Baseline (Day -1) through Day 6 (120 hours post-dose))
- Number of Participants With Clinically Significant Laboratory Abnormalities(Baseline (Day -1) through Day 6 (120 hours post-dose))
- Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score(Baseline (Day -1) through Day 6 (120 hours post-dose))