A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Ipatasertib in Subjects With Mild, Moderate or Severe Hepatic Impairment Compared to Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 3
- 主要终点
- Area Under the Plasma Concentration-Time Curve (AUC) from 0 to Infinity (AUC0-inf) of Ipatasertib
研究概览
简要总结
This is a Phase 1 study evaluating the pharmacokinetics, tolerability and safety of a single dose of ipatasertib in participants with mild, moderate or severe hepatic impairment compared to healthy participants.
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 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •In good health (except for specific inclusion criteria related to hepatic impairment), as determined by the Investigator, based on no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram, and vital signs
- •Females will not be pregnant or breastfeeding, and must be either postmenopausal or agree to use a study-approved method of contraception from the time of signing the informed consent until 30 days after discharge
- •Males will either be sterile or agree to use male condom with spermicide from check-in (Day -1) until 90 days following the dose of study drug
- •Additional Inclusion Criteria for Healthy Subjects Only:
- •Liver enzyme tests must be less than or equal to the upper limits of normal
- •Additional Exclusion Criteria for Hepatic Impaired Subjects Only:
- •Hepatic impairment must have a Child-Pugh score of 5 to 6 (mild), 7 to 9 (moderate), or 10 to 15 (severe) and have stable hepatic insufficiency within 1 month prior to Screening
排除标准
- •History of ulcerative colitis or stomach or intestinal surgery or resection
- •History of unstable diabetes mellitus
- •History of alcoholism or drug addiction within 1 year prior to Check-in (Day -1)
- •Use of oral, implantable, transdermal, or injectable contraceptives from the time of signing the informed consent (females only) or 10 days prior to Check-in through 45 days after the dose administration
- •Poor peripheral venous access
- •Receipt of blood products within 2 months prior to check-in
- •Additional Exclusion Criteria for Healthy Subjects Only:
- •Use of any tobacco- or nicotine-containing products within 6 months prior to check-in and during the entire study
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder
- •Additional Exclusion Criteria for Hepatic Impaired Subjects Only:
- •Any evidence of progressive liver disease that has worsened or is worsening within 1 month prior to the screening visit
- •Participant has shown evidence of hepatorenal syndrome
- •Ascites requiring paracentesis
- •Participant has required treatment for GI bleeding within 12 months prior to Check-in
- •Participant has required additional medication for hepatic encephalopathy within the 12 months (6 months for severe hepatic impairment) prior to check-in
- •Total bilirubin levels >6 mg/dL
研究组 & 干预措施
Normal Hepatic Function
Participants with normal hepatic function will be administered a single oral dose of ipatasertib (100 mg).
干预措施: Ipatasertib (Drug)
Mild Hepatic Impairment
Participants with mild hepatic impairment (Child-Pugh Class A, score of 5 to 6, inclusive) will be administered a single dose of ipatasertib (100 mg).
干预措施: Ipatasertib (Drug)
Moderate Hepatic Impairment
Participants with moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9, inclusive) will be administered a single dose of ipatasertib (100 mg).
干预措施: Ipatasertib (Drug)
Severe Hepatic Impairment
Participants with severe hepatic impairment (Child-Pugh Class C, score of 10 to 15, inclusive) will be administered a single dose of ipatasertib (100 mg).
干预措施: Ipatasertib (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve (AUC) from 0 to Infinity (AUC0-inf) of Ipatasertib
时间窗: up to Day 15
AUC0-inf is defined as AUC extrapolated from Hour 0 to infinity of ipatasertib in the plasma.
Maximum Observed Plasma Concentration (Cmax) of Ipatasertib
时间窗: up to Day 15
Maximum observed concentration of ipatasertib as determined by measuring drug concentration in blood samples over time.
次要结局
- Percentage of Participants with Treatment-Emergent Adverse Events (AE)(up to Day 15)
- Time to Reach Maximum Observed Concentration (tmax) of Ipatasertib(up to Day 15)
- AUC from 0 to last measurable concentration (AUC0-t)(up to Day 15)
- Half-life (t1/2) of Ipatasertib(up to Day 15)
- Apparent Plasma Clearance (CL/F) of Ipatasertib(Up to Day 15)
- Apparent Volume of Distribution (V/F) of Ipatasertib(up to Day 15)