A Phase I, Open-label, Multi-center, Single Dose, Parallel Group Study to Evaluate the Pharmacokinetics and Safety of Osilodrostat (LCI699) in Subjects With Impaired Hepatic Function Compared to Subjects With Normal Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 3
- 主要终点
- PK of a single dose of 30 mg osilodrostat: Cmax
研究概览
简要总结
To assess the pharmacokinetics of a single oral dose of osilodrostat (LCI699) 30 mg in subjects with mild, moderate and severe hepatic impairment compared with subjects with normal hepatic function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Weight ≥50 kg and BMI between 18-38kg/m
- •Stable liver cirrhosis and evidence of hepatic impairment.
- •Free of significant medical disorders unrelated to underlying hepatic impairment
排除标准
- •History of any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs
- •Subjects with ongoing alcohol or drug abuse
- •Symptoms or history of encephalopathy (Grade 2 or above)
- •History or presence of liver disease or liver injury (healthy volunteers only)
- •History or presence of impaired renal function
- •Clinical evidence of severe ascites.
- •Total Bilirubin > 6 mg/dL,
- •Subjects with a serum free cortisol test results that is below the lower limit of normal (based on central laboratory) during the screening period
- •Concomitant use of a drug that is a strong inducer of the CYP3A4/5 pathway
- •Other protocol-defined inclusion/exclusion criteria may apply -
研究组 & 干预措施
osilodrostat (LCI699)
Each participant will undergo a 28-day screening/baseline period (day -28 to day -1), followed by a 5 day treatment period (a single 30 mg dose of LCI699 ( Day 1) with 5 days of PK sample collection).
干预措施: osilodrostat (Drug)
结局指标
主要结局
PK of a single dose of 30 mg osilodrostat: Cmax
时间窗: Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
Pharmacokinetics (PK) of a single dose of 30 mg osilodrostat: AUClast
时间窗: Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: AUCinf
时间窗: Predose (Day 0) , and at imepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: T1/2
时间窗: Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: CL/F
时间窗: Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: Vz/F
时间窗: Predose (Day 0) , and timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
次要结局
- The relationship between PK parameters (Cmax and AUC) and baseline hepatic function parameters namely; total bilirubin, albumin, INR (or prothrombin, if INR unavailable)(Predose ( Day 0) and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.)
- Number of participants with adverse events (AEs)(Pre-treatment, during treatment (Day 1) and 30 days post treatment.)