A Phase I Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Mitiperstat
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Volume of distribution (apparent) following extravascular administration [based on terminal phase] (Vz/F)
研究概览
简要总结
This study will assess the effect of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of mitiperstat.
详细描述
This is a Phase I, single dose, non-randomised, open-label, parallel group study to examine the PK, safety, and tolerability of mitiperstat in participants with hepatic impairment and participants with normal hepatic function.
Participants will be assigned to one of the following cohorts as per Child-Pugh classification:
- Cohort 1: Eight participants with Mild hepatic impairment (Child-Pugh A)
- Cohort 2: Eight participants with Moderate hepatic impairment (Child-Pugh B)
- Cohort 3: Six to eight participants with Severe hepatic impairment (Child-Pugh C)
- Cohort 4: Eight to twelve participants with Normal hepatic function
A final safety follow-up visit on Day 21 will be there after all procedures are completed on Day 15.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥ 18 to ≤ 85 years (inclusive), at the time of signing the informed consent.
- •Weight ≥ 50kg and BMI ≥ 18 kg/m2 up to < 42 kg/m
- •Male and/or females.
- •Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Criterion not applicable to this CSP version.
- •Female participants:
- •Female participants must not be lactating.
- •Female participants of childbearing potential who are sexually active with a non-sterilised male partner must agree to use an acceptable method of birth control, from enrolment throughout the study and until at least 4 weeks after the last dose of study intervention.
- •Capable of giving signed informed consent.
- •Participants with hepatic impairment only:
- •Supporting documents confirming that the participant has liver cirrhosis with hepatic impairment must be available.
- •Diagnosis of chronic and stable hepatic impairment.
排除标准
- •Any positive result on screening for serum or plasma hepatitis B surface antigen, hepatitis C antibody, and HIV.
- •History of substance dependence or a positive screen for drugs of abuse, likely to impact participant safety or compliance with study procedures.
- •History of alcohol abuse or excessive intake of alcohol in the last 12 months.
- •Abnormal vital signs, after 10 minutes supine rest at screening or Day -
- •Any clinically important abnormalities in rhythm, conduction or morphology of the resting 12-lead ECG at screening or Day -1:
- •Vulnerable participants.
- •For female participants only: currently pregnant or breast-feeding.
- •Participants with hepatic impairment only
- •Participants with previous transjugular intrahepatic portosystemic shunt (TIPS).
- •Severe ascites defined as ascites requiring paracentesis and albumin at 4-week intervals or less.
- •Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the screening period.
- •Any evidence of additional severe or uncontrolled systemic disease or laboratory finding that makes it unsafe for the participant to participate in the study.
- •Change in dose regimen of medically-required medication within the last 2 weeks before pre-study examination.
- •Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
- •Clinically relevant hepatic encephalopathy.
- •Oesophageal variceal bleeding in prior 3 months.
- •Platelet count < 50 × 109/L and/or neutrophil count < 1.2 × 109/L and/or haemoglobin < 85 g/L.
- •Post liver transplantation.
- •History of acute or chronic pancreatitis, or pancreatic amylase or lipase greater than twice the ULN at screening.
研究组 & 干预措施
Cohort 1
8 participants with mild hepatic impairment (Child-Pugh A) will be given Dose A of mitiperstat.
干预措施: Mitiperstat (Drug)
Cohort 2
8 participants with moderate hepatic impairment (Child-Pugh B) will be given Dose A of mitiperstat.
干预措施: Mitiperstat (Drug)
Cohort 3
6-8 participants with severe hepatic impairment (Child-Pugh C) will be given Dose A of mitiperstat.
干预措施: Mitiperstat (Drug)
Cohort 4
8-12 participants with normal hepatic function will be given Dose A of mitiperstat.
干预措施: Mitiperstat (Drug)
结局指标
主要结局
Volume of distribution (apparent) following extravascular administration [based on terminal phase] (Vz/F)
时间窗: Day 1 to Day 15
The Vz/F of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
Non-renal clearance of drug from plasma (CLNR)
时间窗: Day 1 to Day 15
The CLNR of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
Maximum observed plasma concentration (Cmax)
时间窗: Day 1 to Day 15
The Cmax of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated and compared.
Area under the concentration-time curve from time zero to last time of quantifiable concentration (AUClast)
时间窗: Day 1 to Day 15
The AUClast of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated and compared.
Time to Cmax (tmax)
时间窗: Day 1 to Day 15
The tmax of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
Percentage of dose excreted unchanged in urine from time 0 to time 24 (fe[0-24)
时间窗: Day 1 to Day 15
The fe(0-24) of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
Area under the concentration-time curve from time zero to infinity (AUCinf)
时间窗: Day 1 to Day 15
The AUCinf of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated and compared.
Apparent terminal elimination half-life (t½λz)
时间窗: Day 1 to Day 15
The t½λz of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
Cumulative amount of unchanged drug excreted into urine (Ae[0-24])
时间窗: Day 1 to Day 15
The Ae(0-24) of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
Apparent Clearance (CL/F)
时间窗: Day 1 to Day 15
The CL/F of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
Renal clearance of drug from plasma (CLR)
时间窗: Day 1 to Day 15
The CLR of a single dose of mitiperstat in participants with impaired hepatic function and controls with normal hepatic function will be evaluated.
次要结局
- Adverse Events (AEs), and Serious Adverse Events (SAEs)(From time of dose to the final follow-up visit (Day 21 [± 4 days]))