A Phase I Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144
A Phase I, Multicentre, Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144
研究概览
详细说明
This Phase I, open-label, parallel group study will investigate the single oral dose PK, safety, and tolerability of AZD4144 to male and female participants with mild, moderate, and severe hepatic impairment compared to matched controls with normal hepatic function.
Approximately 60 participants are planned to be screened to achieve up to 30 evaluable participants. For each of the 3 hepatic impairment groups, 6 participants are planned to complete the study. Initially, 6 participants with normal hepatic function will be recruited, matched on a group level regarding sex, age, and BMI to the participants with hepatic impairment. Additional participants with normal hepatic function, up to a total of 12, may be included if needed to meet the matching criteria.
研究类型
注册 (估计的)
阶段
- 阶段1
联系人和位置
学习联系方式
- 姓名:AstraZeneca Clinical Study Information Center
- 电话号码:1-877-240-9479
- 邮箱:information.center@astrazeneca.com
学习地点
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Arizona
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Mesa、Arizona、美国、85210
- Research Site
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Florida
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Miami Lakes、Florida、美国、33014
- Research Site
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Orlando、Florida、美国、32809
- Research Site
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Texas
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Austin、Texas、美国、78757
- Research Site
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
Healthy Matched Control Participants Only (Group 4):
• Must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.
Hepatically-Impaired Participants Only (Groups 1, 2, and 3):
- Must have a diagnosis of chronic (≥ 6 months) and stable hepatic impairment (e.g., no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study screening, as determined by the investigator at screening and Day -1).
- Must be classified by the investigator as CP Class A (Group 1), CP Class B (Group 2), or CP Class C (Group 3) at screening.
- Participant must be stable on a concomitant medication and/or treatment regimen (defined as not starting a new treatment/medication[s] or a change in the dosage or frequency of the concomitant medication[s] within at least 2 weeks prior to screening).
All Groups:
- Body weight ≥ 50 kg and body mass index (BMI) within the range 18 to 45 kg/m2, inclusive.
- All Females of Childbearing Potential (FOCBP) must have a negative pregnancy test at screening and Day -1.
Exclusion Criteria:
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
- Have Type 1 diabetes mellitus or T2DM (Group 4)
- Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.
- History of long QT syndrome or prolonged QTcF.
- Presence of unstable medical or psychological conditions, or any evidence of additional severe or uncontrolled systemic disease (e.g., currently unstable or uncompensated renal, cardiovascular, or respiratory disease).
- Evidence of renal impairment at screening
- Current liver transplant or anticipated to receive liver transplant within 2 months of screening or Day -1 (Group 1, 2 and 3).
- Use of any of the prescription and non-prescription prohibited medications.
- Concomitant immunosuppressive, steroid treatment.
- Live or attenuated vaccines within 3 months prior to study intervention or live vaccinations planned during the trial.
- History of severe allergy/hypersensitivity of AZD4144 or any of the excipients of the product.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days prior to study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的:第 1 组
轻度肝功能不全的参与者(CP A 级,评分为 5 或 6)
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Single oral dose of AZD4144 in participants from all groups
|
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实验性的:第2组
中度肝功能不全(Child-Pugh B级,评分7至9分)的参与者。
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Single oral dose of AZD4144 in participants from all groups
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实验性的:Group 3
Participants with severe hepatic impairment (CP Class C, score of 10 to 15).
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Single oral dose of AZD4144 in participants from all groups
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实验性的:Group 4
Participants with normal hepatic function matched on a group level regarding sex, age, and BMI to the impaired groups
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Single oral dose of AZD4144 in participants from all groups
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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PK parameters AUCinf
大体时间:Day 0 through Day 7 or 9
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area under the concentration-time curve from zero to infinity
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Day 0 through Day 7 or 9
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PK parameter AUClast
大体时间:Day 0 through Day 7 or 9
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area under the concentration-time curve from zero to the last measurable concentration
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Day 0 through Day 7 or 9
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PK parameters AUC(0-144)
大体时间:Day 0 through Day 7
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area under the curve from time zero to time 144hours post dose
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Day 0 through Day 7
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PK parameter Cmax
大体时间:Day 0 through Day 7 or 9
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maximum observed plasma concentration
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Day 0 through Day 7 or 9
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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PK parameters tmax
大体时间:Day 0 through Day 7 or 9
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time to reach maximum observed plasma concentration
|
Day 0 through Day 7 or 9
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PK Parameters t1/2λz
大体时间:Day 0 through Day 7 or 9
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half-life associated with terminal slope (λz)
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Day 0 through Day 7 or 9
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PK Parameters CL/F
大体时间:Day 0 through Day 7 or 9
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apparent total body clearance of drug from plasma after extravascular administration
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Day 0 through Day 7 or 9
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PK Parameters Vz/F
大体时间:Day 0 through Day 7 or 9
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apparent volume of distribution during the terminal phase after extravascular administration.
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Day 0 through Day 7 or 9
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PK Parameters CLNR/F
大体时间:Day 0 through Day 7 or 9
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non-renal clearance of drug from plasma
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Day 0 through Day 7 or 9
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PK parameters CLR from urine concentrations
大体时间:Day 0 through Day 3
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renal clearance from urine concentration
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Day 0 through Day 3
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PK parameters Ae determined from urine concentration
大体时间:Day 0 through Day 3
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amount of unchanged drug excreted into the urine
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Day 0 through Day 3
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PK parameters fe determined from urine concentration
大体时间:Day 0 through Day 3
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Percentage of unchanged drug excreted into the urine
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Day 0 through Day 3
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PK Parameters tlast
大体时间:Day 0 through Day 7 or 9
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time of last quantifiable concentration
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Day 0 through Day 7 or 9
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PK Parameters λz
大体时间:Day 0 through Day 7 or 9
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terminal elimination rate constant
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Day 0 through Day 7 or 9
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PK Parameters AUC(0-24)
大体时间:Day 0 through Day 1
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area under the plasma concentration-time curve from time 0 to 24 hours postdose
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Day 0 through Day 1
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PK Parameters AUC(0-72)
大体时间:Day 0 through Day 3
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area under the plasma concentration-time curve from time 0 to 72 hours postdose
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Day 0 through Day 3
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合作者和调查者
赞助
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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