Pharmacokinetics and Safety of ABT-493 and/or ABT-530 in Subjects With Normal and Impaired Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 4
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
This is an open-label, single-dose study designed to assess the pharmacokinetics and safety of ABT-493 and/or ABT-530 in subjects with impaired hepatic function and compare them to those in subjects with normal hepatic function.
Twenty-four subjects will be selected and enrolled according to the subject selection criteria: 6 subjects with mild stable chronic hepatic impairment (Group I), 6 subjects with moderate stable chronic hepatic impairment (Group II), 6 subjects with severe stable chronic hepatic impairment (Group III) and 6 subjects with normal hepatic function (Group IV).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •All Subjects
- •If female, subject must be either postmenopausal for at least 2 years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy).
- •Females must have negative results for pregnancy test performed:
- •At Screening on a urine specimen obtained within 28 days prior to initial study drug administration, and
- •On a serum sample obtained on Study Day -1 of Period
- •Males must be surgically sterile or practicing at least one of the following methods of birth control (sperm donation within the study period is not allowed):
- •Abstinence
- •Partner(s) using an Intrauterine Device (IUD)
- •Partner(s) using oral, injected, or implanted methods of hormonal contraceptives
- •Subject and/or partner(s) using double-barrier method.
- •Subjects with Normal Hepatic Function
- •In addition to the inclusion criteria above for all subjects, the following criteria must be met for subjects with normal hepatic function enrolled in Group IV:
- •Judged to be in general good health based upon the results of a medical history, physical examination, laboratory profile (including liver function parameters within the limits of normal) and 12-lead electrocardiogram (ECG).
- •Negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV Ab) test results.
- •Body Mass Index (BMI) is ≥ 18 to < 38 kg/m2, inclusive.
- •Subjects with Hepatic Impairment
- •In addition to the inclusion criteria for all subjects, the following criteria must be met for all subjects with hepatic impairment enrolled in Groups I, II and III:
- •Judged to be in stable condition and acceptable for study participation based upon the results of a medical history, physical examination, laboratory profile and ECG.
- •BMI is ≥ 18 to < 38 kg/m2, inclusive, for subjects with hepatic impairment without ascites or subjects with subclinical ascites detected only by ultrasound or other imaging. For subjects with hepatic impairment and clinically significant ascites, BMI is permitted in the range between ≥ 18 to < 40 kg/m2, inclusive.
- •Child-Pugh classification of Categories A (mild), B (moderate), or C (severe).
- •Medical history of chronic liver disease including and not limited to chronic hepatitis B, history of alcoholic liver disease and chronic hepatitis C.
- •Presence of clinically significant hepatic impairment as indicated by either:
- •Evidence of liver cirrhosis OR
- •Medical history of at least one of the following criteria:
- •Clinical diagnosis of liver disease
- •Total bilirubin, > 2 mg/dl, with indirect/direct ratio < 1 or prolonged prothrombin time elevation > 1.7 or an albumin value below the lower limit of the laboratory reference range and excluding non-hepatic causes of the previous laboratory abnormalities.
排除标准
- •History of significant sensitivity to any drug.
- •Pregnant or breastfeeding female.
- •Recent (6-month) history of drug or alcohol abuse.
- •Positive test result for hepatitis A virus immunoglobulin M (HAV-IgM) or human immunodeficiency virus antibody (HIV Ab). Negative HIV status will be confirmed at Screening and the results will be maintained confidentially by the study site.
- •Detectable HCV RNA.
研究组 & 干预措施
Group I
Subjects with mild hepatic impairment
干预措施: ABT-530 (Drug)
Group I
Subjects with mild hepatic impairment
干预措施: ABT-493 (Drug)
Group II
Subjects with moderate hepatic impairment
干预措施: ABT-493 (Drug)
Group II
Subjects with moderate hepatic impairment
干预措施: ABT-530 (Drug)
Group III
Subjects with severe hepatic impairment
干预措施: ABT-493 (Drug)
Group III
Subjects with severe hepatic impairment
干预措施: ABT-530 (Drug)
Group IV
Subjects with normal hepatic function
干预措施: ABT-493 (Drug)
Group IV
Subjects with normal hepatic function
干预措施: ABT-530 (Drug)
结局指标
主要结局
Number of subjects with adverse events
时间窗: Up to 58 days
Overall measurement of pharmacokinetic parameter values of ABT-493 and ABT-530
时间窗: 7 days
Pharmacokinetic parameter values include the maximum plasma concentration (Cmax), the terminal phase elimination rate constant (B), the area under the plasma concentration-time curve (AUC) from time 0 to time of the last measurable concentration (AUCt).
Overall measurement of safety parameters
时间窗: Up to 38 days
Measurement of safety parameters include physical examinations, clinical laboratory tests, 12-lead ECGs (electrocardiograms) and vital signs.
次要结局
未报告次要终点