A Single Dose, Non-randomised, Open-label, Parallel Group Study to Assess the Pharmacokinetics, Safety, and Tolerability of AZD4144 in Participants With Severe Renal Impairment, End-stage Kidney Disease, and in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Observed maximum plasma concentration (Cmax)
研究概览
简要总结
A study to investigate the pharmacokinetics, safety, and tolerability of AZD4144 in participants with severe renal impairment, end-stage kidney disease, and in healthy participants.
详细描述
This is an open-label, single dose, non-randomised, parallel group, Phase I study to assess the pharmacokinetics, safety, and tolerability of AZD4144 in male and female participants with severe renal impairment and end-stage kidney disease (ESKD) compared with healthy control participants.
The study will comprise of:
- A Screening Period of 21 days.
- Cohort 1, 2, 4, and 5: a single Treatment Period with an in-clinic period of 7 days.
- Cohort 3: two Treatment Periods each with an in-clinic period of 7 days, and a washout period of 6 days after the in-clinic treatment period.
- A Follow-up visit 7 days following discharge.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Matched Control Participants Only (Cohort 2):
- •Stable renal function (for example, no clinically significant change in an estimated glomerular filtration rate (eGFR) within 3 months or longer prior to study the Screening Visit), as determined by the investigator.
- •Have an eGFR of ≥ 90 milliliter/minute/1.73m2 (mL/min/1.73m2) as determined via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula without race.
- •Renally Impaired Participants Only (Cohorts 1, 4 and 5)
- •Participants who have renal impairments.
- •Cohort 1 participants with severe renal impairment must have an eGFR ≥ 15 to < 30 mL/min/1.73m2 not on dialysis. Cohort 1 should have at least 3 participants with eGFR ≤ 20 mL/min/1.73m
- •Cohort 4 participants with moderate renal impairment must have an eGFR of ≥ 30 to < 60 mL/min/1.73m
- •Cohort 5 participants with mild renal impairment must have an eGFR of ≥ 60 to < 90 mL/min/1.73m
- •Participants with ESKD on IHD must have been on stable IHD for at least 3 months prior to Visit
- •All renally impaired participants should be on stable standard of care for at least 4 weeks prior to Visit
- •All cohorts:
- •Body weight of at least 50 kilograms (kg) and body mass index (BMI) within the range ≥ 18 to ≤ 35 kg/m2, inclusive.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
排除标准
- •History of QT prolongation associated with other medications that required discontinuation of that medication.
- •Congenital long QT syndrome.
- •Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.
- •Concomitant immunosuppressive, steroid treatment.
- •Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment) (Cohort 2).
- •Renal transplant participants, participants on dialysis, and those with a history of acute kidney injury (Cohorts 1, 4, 5).
- •Use of any of the prohibited medications in the 4 weeks prior to Visit 1 (Cohorts 1, 3, 4, 5).
- •Participants with a known hypersensitivity to AZD4144 or any of the excipients of the product.
研究组 & 干预措施
Cohort 1: AZD4144
Participants with severe renal impairment will receive a single oral dose of AZD4144 on Day 1.
干预措施: AZD4144 (Drug)
Cohort 2: AZD4144
Healthy participants with normal renal function will receive a single oral dose of AZD4144 on Day 1.
干预措施: AZD4144 (Drug)
Cohort 3: AZD4144
Participants with ESKD on intermittent haemodialysis will receive a single oral dose of AZD4144 on the first day of Treatment Period 1 and Treatment Period 2.
干预措施: AZD4144 (Drug)
Cohort 4: AZD4144
Participants with moderate renal impairment will receive a single oral dose of AZD4144 on Day 1.
干预措施: AZD4144 (Drug)
Cohort 5: AZD4144
Participants with mild renal impairment will receive a single oral dose of AZD4144 on Day 1.
干预措施: AZD4144 (Drug)
结局指标
主要结局
Observed maximum plasma concentration (Cmax)
时间窗: From Day 1 to Day 14
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf)
时间窗: From Day 1 to Day 14
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
时间窗: From Day 1 to Day 14
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Apparent total body clearance (CL/F)
时间窗: From Day 1 to Day 14
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Non-renal clearance of drug from plasma (CLNR/F)
时间窗: From Day 1 to Day 14
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Apparent volume of distribution based on the terminal phase (Vz/F)
时间窗: From Day 1 to Day 14
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Terminal elimination half-life (t½λz)
时间窗: From Day 1 to Day 14
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Renal clearance of drug from plasma (CLR)
时间窗: From Day 1 to Day 4
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Amount excreted (Ae)
时间窗: From Day 1 to Day 4
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Percentage of dose excreted unchanged in urine (fe)
时间窗: From Day 1 to Day 4
To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
次要结局
- Number of Treatment Emergent Adverse Events (TEAEs)(From Day 1 to Follow-up (Day 14/28))