Open-label, Single-dose, Parallel-group Study to Compare the PKs of Iloperidone in Subjects With Mild or Moderate Hepatic Impairment With That in Matched Healthy Control Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Measure: Area Under Curve (AUClast, AUCinf) and maximum concentration (Cmax)
研究概览
简要总结
This study aims to determine the pharmacokinetic profile and the tolerability of iloperidone in subjects with mild or moderate hepatic impairment comparatively to healthy matched subjects
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria (all subjects):
- •Caucasian subjects
- •Inclusion criteria (hepatic impaired subjects):
- •subjects with physical signs consistent with a clinical diagnosis of stable liver disease, which has been confirmed by imaging techniques, ultrasound, Magnetic Resonance Imaging or Computed Tomogram within 3 months of screening, and a creatinine clearance > 50 mL/min (based on Cockroft and Gault formula).
- •Inclusion criteria (healthy volunteers):
- •good general health
- •matched by age, gender, smoking status, Body Mass Index, and CYP2D6 phenotype to hepatic impaired subjects.
排除标准
- •Exclusion criteria (all subjects):
- •Subjects who report smoking a pipe, cigars or more than 20 cigarettes per day .
- •History of drug abuse as defined in Diagnostic and Statistical Manual of Mental Disorders, Diagnostic Criteria for Drug and Alcohol Abuse, within the 12 months prior to screening
- •History of first-dose response/syncope to alpha1-blocking agents
- •Exclusion criteria (Hepatic impaired subjects):
- •Patients with symptoms or 6 months past history of encephalopathy.
- •Patients with clinical evidence of moderate-severe ascites.
- •Patients having a previous surgical porto-systemic shunt.
- •Exclusion criteria (Healthy volunteers):
- •History of alcohol abuse prior to dosing, or evidence of such abuse during screening.
- •Pulse Rate > 200 msec
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Iloperidone
Eligible subjects receive a single oral dose of 2 mg iloperidone as a tablet
干预措施: Iloperidone (Drug)
结局指标
主要结局
Measure: Area Under Curve (AUClast, AUCinf) and maximum concentration (Cmax)
时间窗: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose
Pharmacokinetics of iloperidone in subjects with mild or moderate hepatic impairment, compared to healthy volunteers.
Maximum plasma concentration following drug administration (Cmax) of iloperidone
时间窗: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose, and from pre-dose to 48 hours post-dose
Blood and urine samples will be collected and plasma and urine concentration will be measured.
Protein binding of iloperidone
时间窗: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose, and from pre-dose to 48 hours post-dose
Blood samples will be collected and protein binding will be measured .
Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone
时间窗: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose, and from pre-dose to 48 hours post-dose
Blood and urine samples will be collected and plasma and urine concentration will be measured.
次要结局
- Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone metabolite P88 records, listed by subject. Summary statistics provided by impairment group and visit/time.(pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose)
- Maximum plasma concentration following drug administration (Cmax) of iloperidone metabolites P88(pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose)
- Protein binding of iloperidone metabolites P88 (CLr)(pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose)
- Area Under the plasma Curve (AUC) of iloperidone metabolite P95(pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose)
- Area under the plasma concentration-time Curve from time zero to infinity (AUCinf) of iloperidone metabolite P95(pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose)
- Maximum plasma concentration following drug administration (Cmax) of iloperidone metabolites P95(pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose)
- Protein binding of iloperidone metabolites P95(pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose)
- Number of participants with adverse events(Day 6)
- Area Under the plasma Curve (AUC) of iloperidone metabolite P88(pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 hours post-dose and from pre-dose to 48 hours post-dose)