An Open-Label Study to Characterize the Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of PSI-7977 or PSI-352938 in HCV-infected Subjects With Varying Degrees of Hepatic Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 主要终点
- Pharmacokinetic data derived from plasma samples collected over 7 days
研究概览
简要总结
This study will be conducted in Hepatitis C positive patients to determine whether the pharmacodynamic effects of PSI-7977 or PSI-352938 are similar to HCV-infected patients with normal hepatic function, which may allow inclusion of patients with cirrhosis and varying degrees of hepatic dysfunction in future clinical studies.
详细描述
This study is designed per the Food and Drug Administration (FDA) guidance for patients with impaired hepatic function to assess the influence of hepatic impairment on the PK and pharmacodynamics (PD) of PSI-7977 and PSI-352938 This study will be conducted in Hepatitis C positive patients to ascertain whether the PD effects of PSI-7977 or PSI-352938 are similar to HCV-infected patients with normal hepatic function, which may allow inclusion of patients with cirrhosis and varying degrees of hepatic dysfunction in future clinical studies. Data from subjects who participated in the P2938-0212 study (PSI-352938 MAD) will be used as the control group. These subjects were documented non-cirrhotic subjects with normal hepatic function. Hepatitis C Virus (HCV) Genotypes 1-6 will be enrolled in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hepatic impaired Males or females of non-childbearing potential aged > 18 years with Chronic HCV-infection
- •Naïve to all direct acting anti-viral (DAA) treatments for chronic HCV infection.
- •Documented Cirrhosis
排除标准
- •Prior PEG/RBV null responders.
- •Unstable cardiac disease, recent Myocardial infarction, or family history of QTc prolongation or unexplained cardiac arrest.
- •Positive test at Screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or anti-human immunodeficiency virus (HIV) Ab.
- •History of clinically significant medical condition associated with other chronic liver disease
- •Any current signs or symptoms of severe hepatic encephalopathy
- •History of gastric or esophageal variceal bleeding in which varices have not been adequately treated with medication and surgical procedures
- •Prior placement of a portosystemic shunt
- •History of hepatorenal, or hepatopulmonary syndrome.
- •Active spontaneous bacterial peritonitis.
- •Use of medications associated with QT prolongation within 28 days prior to dosing.
- •Current Hypotension
- •History of Torsades de Pointes, evidence of an active or suspected cancer, or a history of malignancy, Abnormal hematological and biochemical parameters
研究组 & 干预措施
PSI-352938 Group A
Mild (Child-Pugh Class A; 5-6) hepatic impairment
干预措施: PSI-352938 (Drug)
PSI-352938 Group B
Moderate (Child-Pugh Class B; 7-9) hepatic impairment
干预措施: PSI-352938 (Drug)
PSI-352938 Group C
Severe (Child-Pugh Class C; 10-15) hepatic impairment
干预措施: PSI-352938 (Drug)
PSI-7977 Group A
Mild (Child-Pugh Class A; 5-6) hepatic impairment
干预措施: PSI-7977 (Drug)
PSI-7977 Group B
Moderate (Child-Pugh Class B; 7-9) hepatic impairment
干预措施: PSI-7977 (Drug)
PSI-7977 Group C
Severe (Child-Pugh Class C; 10-15) hepatic impairment
干预措施: PSI-7977 (Drug)
结局指标
主要结局
Pharmacokinetic data derived from plasma samples collected over 7 days
时间窗: 28 time points over Seven Days
To characterize the pharmacokinetics (PK) of PSI-352938 over 7 days of dosing with PSI-352938 in HCV-infected patients with varying degrees of hepatic impairment compared to historical PK data.
Pharmacokinetic comparison with historical data over 7 days of dosing with PSI-7977
时间窗: Seven Days
To characterize the PK of PSI-7977 and metabolites over 7 days of dosing with PSI-7977 in HCV-infected patients with varying degrees of hepatic impairment compared to historical PK data.
次要结局
- Viral dynamics/ changes in HCV (ribonucleic acid) RNA(Baseline through follow-up (post-Day 14))
- Dosage adjustment in hepatically impaired patients(Seven days)
- Number and severity of adverse events(Seven Days)
- Changes in genotypic or phenotypic measurements(Seven Days)