A Phase I Study to Assess the Safety and Pharmacokinetics of Telaprevir (VX-950) in Subjects With Moderate and Severe Hepatic Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 主要终点
- Comparing the area under the plasma concentration-time curve (AUC8h) of telaprevir in patients of Group 2 and Group 1
研究概览
简要总结
The purpose of this study is to determine whether the pharmacokinetic (what the body does to the drug) parameters of telaprevir are altered in patients with moderate hepatic impairment, compared to the pharmacokinetic parameters in patients with normal liver function, and measure the relative unbound plasma concentrations of telaprevir.
详细描述
This is a Phase I, open-label (all people know the identity of the intervention) study to investigate the single dose and steady state pharmacokinetics of telaprevir in patients with moderate hepatic impairment, and measure the relative unbound plasma concentrations of telaprevir. In addition, a small group of patients with severe hepatic impairment will be included to further characterize the pharmacokinetics of telaprevir as a function of liver disease. In this study 24 patients will be enrolled. Based upon physical examination and laboratory assessments, patients will be scored and classified into hepatic function groups on the basis of the Child-Pugh classification (Classification is based on Child-Pugh score which is used to assess prognosis of chronic hepatic disease). A Child-Pugh score of 7 to 9 is considered Child-Pugh category B (CPB) and indicative of moderate liver function impairment; a Child-Pugh score of 10 or greater is considered Child Pugh category C (CPC), indicative of severe liver impairment. Hepatic function groups will consists of Group 1: 10 patients with moderate hepatic impairment (CPB 7 to 9]); Group 2: 10 healthy control patients with normal hepatic function. Each healthy control patient is matched to a patient in Group 1 with respect to sex, age (+5 years or -5 years) and body mass index (BMI) (+15% or -15%); Group 3: 4 patients with severe hepatic impairment (CPC [limited to Child Pugh score 10 to 12]). Safety and tolerability evaluations including adverse events, clinical laboratory tests, 12-lead electrocardiogram, vital signs and physical examination will be recorded throughout the study period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •For Group 1:
- •Moderate liver function impairment (Child Pugh score of 7 to 9)
- •History of hepatic disease, such as hepatitis B, previous hepatitis C, alcoholic liver disease, autoimmune hepatitis, non-alcoholic fatty liver disease, hereditary/metabolic, cryptogenic, other
- •Consistent with the disease process of hepatic impairment and associated symptoms
- •For Group 2:
- •Matched to a patient with moderate hepatic impairment with regards to sex, age (± 5 years), and BMI (± 15%) and healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality
- •For Group 3:
- •Severe liver function impairment (limited to Child Pugh score of 10 to 12)
- •Hepatic impairment due to different etiologies such as hepatitis B, previous hepatitis C, alcoholic liver disease, autoimmune hepatitis, non-alcoholic fatty liver disease, hereditary/metabolic, cryptogenic, other
- •Consistent with the disease process of hepatic impairment and associated symptoms
排除标准
- •For Group 1 and 3:
- •Has acute infectious hepatitis
- •Has grade 3 or 4 encephalopathy
- •Has grade 3 or 4 creatinine elevation
- •Is an active candidate for liver transplantation
- •Has had variceal bleeding or spontaneous bacterial peritonitis
- •For Group 1 only:
- •Has a porta-caval shunt or transjugular intrahepatic porto-systemic shunts
- •For Group 2:
- •Has acute hepatitis A or hepatitis B or hepatitis C infection
研究组 & 干预措施
Group 1
10 patients with moderate hepatic impairment (CPB [Child-Pugh score 7 to 9])
干预措施: telaprevir (Drug)
Group 2
10 healthy control patients with normal hepatic function. Each healthy control patient is matched to a patient in Group 1 with respect to sex, age (± 5 years) and body mass index (BMI) (± 15%)
干预措施: telaprevir (Drug)
Group 3
up to 4 patients with severe hepatic impairment (CPC [limited to Child Pugh score 10 to 12])
干预措施: telaprevir (Drug)
结局指标
主要结局
Comparing the area under the plasma concentration-time curve (AUC8h) of telaprevir in patients of Group 2 and Group 1
时间窗: Day 1 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), Day 2 to Day 5 (predose), Day 6 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), and Day 7 (24 hour)
The pharmacokinetic parameter AUC8h will be measured from time of administration up to 8 hours post dose of telaprevir following administration of single and multiple oral doses of telaprevir in patients with moderate hepatic impairment (CPB) ie, Group 1, as compared to matched healthy patients ie, Group 2
Comparing the maximum plasma analyte concentration (Cmax) of telaprevir in patients of Group 2 and Group 1
时间窗: Day 1 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), Day 2 to Day 5 (predose), Day 6 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), and Day 7 (24 hour)
The pharmacokinetic parameter Cmax of telaprevir following administration of single and multiple oral doses of telaprevir in patients with moderate hepatic impairment (CPB \[Child-Pugh score 7 to 9\]) ie, Group 1, as compared to matched healthy patients ie, Group 2
Comparing the actual sampling time to reach the maximum plasma analyte concentration (tmax) of telaprevir in patients of Group 2 and Group 1
时间窗: Day 1 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), Day 2 to Day 5 (predose), Day 6 (-1 hour, predose, 0, 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 9, 12, 15, 18 hours postdose), and Day 7 (24 hour)
The pharmacokinetic parameter tmax will be measured following administration of single and multiple oral doses of telaprevir in patients with moderate hepatic impairment (CPB) ie, Group 1, as compared to matched healthy patients ie, Group 2
次要结局
- Number of adverse events in Group 1 patients as a measure of safety(up to Day 6)
- Comparing unbound fractions of telaprevir in patients of Group 1 and Group 2(up to Day 6)
- Comparing any relationship between the measures of hepatic function and selected pharmacokinetic parameters of telaprevir in patients of Group 1 and Group 2(up to Day 6)