An Open-label Parallel-Group Study to Evaluate Pharmacokinetics of E7090 and Its Metabolite in Subjects With Mild and Moderate Hepatic Impairment Compared to Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 8
- 主要终点
- Cmax: Maximum Observed Plasma Concentration of Tasurgratinib
研究概览
简要总结
The primary purpose of the study is to evaluate the effects of mild and moderate hepatic impairment on PK of tasurgratinib after a single dose administration.
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
- 20 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) between 18 to 40 kilogram per square meter (kg/m^2).
- •For Cohorts A and B: stable hepatic impairment conforming to Child-Pugh classification A and B.
- •For Cohort C: healthy participants matched to participants with hepatic impairment with regard to age (+/-10 years), body weight (+/-20 percent [%]), race and gender, and as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiogram (ECG), and clinical laboratory determinations.
排除标准
- •Key Exclusion for all Participants:
- •Following ocular disorders
- •Current evidence of Grade 2 or higher corneal disorder
- •Current evidence of active macular disorder (example, Age-related macular degeneration, central serous chorioretinal disease)
- •Known to be human immunodeficiency virus (HIV) positive at Screening.
- •A prolonged QT/QTc interval ([QT interval using Fridericia's formula] QTcF greater than (>) 480 millisecond [ms]) demonstrated on ECG.
- •Additional Exclusion Criteria for Hepatically Impaired Participants (Cohorts A and B)
- •In addition to the Exclusion Criteria above for all participants, other standard exclusion criteria for participants with hepatic impairment will be used. These include:
- •Any significant acute medical illness (such as new conditions or exacerbation of pre-existing conditions) within 8 weeks of dosing.
- •Presence of severe ascites, edema, or uncontrolled hepatic encephalopathy
- •The participant's standard therapy/concomitant medication for diseases related to hepatic disease has not remained stable/unchanged for at least two weeks before dosing of study drug.
- •Additional Exclusion Criteria for Healthy participants (Cohort C)
- •In addition to the Exclusion Criteria for all participants, other standard exclusion criteria for healthy participants in Phase 1 studies will be used. These include:
- •Syphilis as demonstrated by positive serology at Screening.
- •Any abnormal finding based on physical examination, assessment of vital signs, ECG, or laboratory test results that requires treatment or clinical follow up based on investigators opinion.
研究组 & 干预措施
Cohort A: Mild Hepatic Impairment (Child Pugh Class A)
Participants with mild hepatic impairment will receive a single 35 milligram (mg) tablet of tasurgratinib in the morning with 150 milliliters (mL) of water following an overnight fast of at least 10 hours.
干预措施: Tasurgratinib (Drug)
Cohort B: Moderate Hepatic Impairment (Child Pugh Class B)
Participants with moderate hepatic impairment will receive 10 mg dose of tasurgratinib as capsule (2 capsules each of 5 mg) in the morning with 150 mL of water following an overnight fast of at least 10 hours.
干预措施: Tasurgratinib (Drug)
Cohort C: Healthy Participants (Control)
Healthy participants matched to participants with hepatic impairment in Cohorts A and B (matched with regards to age, race, gender and body weight) will receive a single 35 mg tablet of tasurgratinib in the morning with 150 mL of water following an overnight fast of at least 10 hours.
干预措施: Tasurgratinib (Drug)
结局指标
主要结局
Cmax: Maximum Observed Plasma Concentration of Tasurgratinib
时间窗: Day 1: 0-144 hours postdose
AUC(0-inf): Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of Tasurgratinib
时间窗: Day 1: 0-144 hours postdose
AUC(0-t): Area Under the Plasma Concentration versus Time Curve from Time 0 to Time of Last Quantifiable Concentration of Tasurgratinib
时间窗: Day 1: 0-144 hours postdose
次要结局
- T1/2: Terminal Phase Plasma Half-life of Tasurgratinib and its Metabolite(Day 1: 0-144 hours postdose)
- AUC(0-72Hours): Area Under the Plasma Concentration versus Time Curve from Time 0 to 72 Hours of Tasurgratinib and its Metabolite(Day 1: 0-144 hours postdose)
- fu: Plasma Protein Unbound Fraction of Tasurgratiniband its Metabolite(Day 1: 0-144 hours postdose)
- CLu/F: Apparent Clearance Relative to the Unbound Plasma Concentration of Based on AUCu of Tasurgratinib(Day 1: 0-144 hours postdose)
- CL/F: Apparent Total Body Clearance of Tasurgratinib(Day 1: 0-144 hours postdose)
- Vz/F : Apparent Volume of Distribution at Terminal Phase of Tasurgratinib(Day 1: 0-144 hours postdose)
- AUC Metabolite Ratio: Ratio of AUC(0-inf) of M2 to AUC(0-inf) of Tasurgratinib, Corrected for Molecular Weights(Day 1: 0-144 hours postdose)
- AUCu: AUC(0-inf) Values Adjusted by Unbound Fraction in Plasma of Tasurgratinib(Day 1: 0-144 hours postdose)
- Tmax: Time to Reach Maximum Plasma Concentration of Tasurgratinib and its Metabolite(Day 1: 0-144 hours postdose)