A Phase I, Single-Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- AUClast
研究概览
简要总结
This is a Phase I, multi-centre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD0780 in male and female participants (females of non-childbearing potential) with severe renal impairment not on dialysis, end-stage renal disease (ESRD) on intermittent haemodialysis (HD), or moderate renal impairment (optional) compared with male and female participants (females of non-childbearing potential) with normal renal function. Potential participants will be screened to assess their eligibility to enter the study up to 4 weeks prior to administration of study intervention. Eligible participants will be admitted to the study site on Day -1. On Day 1, an "A" single oral dose of AZD0780 will be administered, and participants will be confined to the study site until after assessments are completed on Day 11.
详细描述
This is a Phase I, multi-centre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD0780 in male and female participants (females of non-childbearing potential) with severe renal impairment not on dialysis, end-stage renal disease (ESRD) on intermittent haemodialysis (HD), or moderate renal impairment (optional) compared with male and female participants (females of non-childbearing potential) with normal renal function.
Participants will be assigned to the following groups based on body surface area-adjusted estimated glomerular filtration rate (eGFR) determined by a local laboratory at screening by the Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation (2021) using serum creatinine:
Group 1: Participants with severe renal impairment (eGFR < 30 mL/min), not on dialysis.
Group 2: Participants with ESRD (eGFR < 15 mL/min) on a stable intermittent HD schedule for at least 3 months prior to planned dosing.
Group 3: Participants with normal renal function demographically matched by sex,age, and body mass index (BMI) to the impaired participants (eGFR of ≥90 mL/min).
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
- 是
入选标准
- •Participant must be 18 to 85 years of age, inclusive at the time of signing ICF
- •For Participants with normal renal function:
- •Participant 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
- •For Participants with renal impairment:
- •Diagnosis of chronic kidney disease, stable renal function in the 6 months prior to dosing
- •Received HD for chronic renal failure for at least 3 months prior to dosing (Group 2)
- •Participants with renal impairment, as follows, based on CKD-EPI equation (BSA-adjusted eGFR) at screening: Group1 eGFR < 30 mL/min), not requiring dialysis, Group 2 ESRD (eGFR < 15 mL/min) on a stable intermittent HD schedule for at least 3 months prior to planned dosing and Group 4 (optional) moderate renal impairment (eGFR ≥ 30 to < 60 mL/min)
- •Male participants:
- •Males must be surgically sterile or using, in conjunction with their female partner, a highly effective method of contraception for the duration of the study (from the time of study intervention administration) until 3 months after discharge to prevent pregnancy in a partner.
- •Female participants of non-childbearing potential:
- •Female participants must not be pregnant and must have a negative pregnancy test at screening and check-in, must not be lactating, and must not be of childbearing potential.
排除标准
- •For Participants with normal renal function:
- •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).
- •Use of any prescription or non-prescription drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before study intervention, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
- •History of any major surgical procedure within 30 days prior to study intervention.
- •For Participants with renal impairment:
- •Presence of unstable medical or psychological conditions which, in the opinion of the investigator, would compromise the participant's safety or successful participation in this study.
- •Renal transplant patients (participants on HD with non-functioning renal transplants are not excluded), participants waiting for organ transplant scheduled to occur during the study, and those with a history of acute kidney injury occurring within 3 months prior to screening.
- •History of any major surgical procedure within 30 days prior to study intervention.
- •Current or previous treatment with drugs for reduction or inhibition of PCSK9 (eg, evolocumab, alirocumab, or inclisiran).
- •Use of moderate/strong inhibitors or inducers of CYP3A4/
- •Unable to refrain from potassium binders, phosphate binders (eg, aluminium hydroxide and calcium carbonate), cholestyramine/colestipol, and ranitidine/nizatidine within 10 hours before and 10 hours after study intervention.
- •Receiving or has received within 14 days of screening, medication that contains a black box warning for significant QT prolongation. A list of prohibited medications can be found in protocol.
- •Use of concurrent medication which affects calculation of eGFR by affecting serum creatinine (eg, cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, or quinine) within 7 days of Day -1.
研究组 & 干预措施
Group 4 (optional): AZD0780
Participants with moderate renal impairment (eGFR ≥ 30 to < 60 mL/min).
干预措施: AZD0780 (Drug)
Group 1: AZD0780
Participants with severe renal impairment (eGFR < 30 mL/min), not on dialysis.
干预措施: AZD0780 (Drug)
Group 2: AZD0780
Participants with ESRD (eGFR < 15 mL/min) on a stable intermittent HD schedule for at least 3 months prior to planned dosing.
干预措施: AZD0780 (Drug)
Group 3: AZD0780
Participants with normal renal function demographically matched by sex, age, and body mass index (BMI) to the impaired participants (eGFR of ≥ 90 mL/min)
干预措施: AZD0780 (Drug)
结局指标
主要结局
AUClast
时间窗: From Day 1 to Day 11
Area under the concentration-time curve from zero to the last measurable concentration
Cmax
时间窗: From Day 1 to Day 11
Maximum observed plasma concentration
AUCinf
时间窗: From Day 1 to Day 11
Area under the concentration-time curve from zero to infinity
次要结局
- Number of participants with adverse events (AEs)(From Day 1 to Day 11)
- Number of participants with abnormal vital signs, abnormal ECGs, and abnormal physical examination findings(From Day 1 to Day 11)
- Number of participants with abnormal laboratory test results(From Day 1 to Day 11)
- PK parameters Tmax(From Day 1 to Day 11)
- PK parameters t1/2λz(From Day 1 to Day 11)
- PK parameters CL/F(From Day 1 to Day 11)
- PK parameters CLNR/F(From Day 1 to Day 11)
- PK parameters Vz/F(From Day 1 to Day 11)
- PK parameters AUC0-96(From Day 1 to Day 11)
- PK parameters CLr(From Day 1 to Day 11)
- PK parameters Ae(From Day 1 to Day 11)
- PK parameters Fe(From Day 1 to Day 11)