A Phase I, Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Study to Assess the Safety, Tolerability, and Pharmacodynamics of AZD4144 in Participants With Established Atherosclerotic Cardiovascular and Chronic Kidney Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and the pharmacodynamics (PD) of AZD4144 following oral administration in participants with atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD).
详细描述
This is a Phase 1b, randomized, double blind, placebo-controlled study and will be conducted in participants with established ASCVD and CKD with persistent inflammation (High-sensitivity C-reactive protein [hsCRP] > 2 mg/L and eGlomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73m2). The participants will be randomized in the 1:1 ratio to either receive treatment with AZD4144 or placebo.
The study will be comprised of:
- A screening period of 28 days
- Treatment period where each participant will either receive oral dose of AZD4144 or placebo for 28 days.
- A follow-up visit (Day 35 ±1) and a Final Follow-up (on Day 56±1) post first dose administration.
The total duration of the study will be approximately 12 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 否
入选标准
- •Participants with established ASCVD history of one or more of the following
- •Prior Myocardial infarction (MI) (>60 days from index event) or coronary revascularization procedure like coronary stenting or Coronary artery bypass graft (CABG)
- •Prior ischemic stroke (>60 days from index event)
- •Symptomatic Peripheral Arterial Disease
- •Chronic kidney disease defined as eGlomular filtration rate (eGFR) ≥ 30 to < 60 mL/min/1.73 m2
- •Serum hsCRP > 2 mg/L
- •Body mass index ≥ 18 to ≤ 45 kg/m2
- •All females must have a negative pregnancy test at the Screening Visit and at the randomization visit
- •Sexually active male participants with partner of childbearing potential must adhere to the contraception methods
- •Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception
- •Females of non-childbearing potential must be confirmed at the Screening visit
排除标准
- •History of malignancy within the last 5 years
- •History of MI, coronary revascularization, stroke or revascularization for peripheral arterial disease in the 60 days prior to Screening
- •Active systemic infection within 30 days
- •Clinically significant active and chronic infections within 60 days prior to randomization
- •Clinically significant recurrent infection (≥ 2× during the last 12-month period).
- •Renal transplant participants, participants on dialysis, and those with a history of acute kidney injury in the past 12 month
研究组 & 干预措施
AZD4144
Participants will receive oral dose of AZD4144 for 28 days.
干预措施: AZD4144 (Drug)
Placebo
Participants will receive oral dose of Placebo for 28 days.
干预措施: Placebo (Other)
结局指标
主要结局
Number of participants with adverse events
时间窗: From first dose (Day 1) until Follow-up (Day 56±1)
The safety and the tolerability of AZD4144 compared with placebo will be evaluated.
Relative change from baseline to 4 weeks in systemic Interleukin-6 (IL-6) levels
时间窗: Day 1 to Day 28
The effect of AZD4144 on circulating inflammatory biomarker IL-6 compared with placebo will be evaluated.
次要结局
- Relative change from baseline to 4 weeks in systemic IL-18 and High-sensitivity C-reactive protein (hsCRP) levels(Day 1 to Day 28)
- Maximum plasma drug concentration (Cmax)(Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose))
- Time to reach maximum observed concentration (tmax)(Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose))
- Observed lowest concentration before the next dose is administered (Ctrough)(Day 1 to Day 28 (pre-dose), Day 1 and Day 22±1 (post-dose))