A 12-week, Randomized, Single-blind, Placebo-controlled, Multi-centre, Parallel Group, Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of Oral AZD5718 After 4 and 12-weeks of Treatment in Patients With Coronary Artery Disease (CAD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 129
- 试验地点
- 1
- 主要终点
- Change From Baseline in Creatinine-normalized u-LTE4 at Week 4
研究概览
简要总结
This is a randomized, single-blind, placebo-controlled, parallel-group, multicentre study in patients with CAD. The study will be conducted at approximately 10 centres in 3 countries. Approximately 138 CAD patients will be randomized to AZD5718 or placebo (treatment duration 12 weeks).
详细描述
This is a randomized, single-blind, placebo-controlled, parallel-group, multicentre study in patients with CAD. The study will be conducted at approximately 10 centres in 3 countries (Denmark, Finland and Sweden).
Patients suitable for the study will be identified and screened for eligibility after being hospitalized for Acute Coronary Syndrome (ACS) (Visit 1) comprising ST Elevation Myocardial Infarction (STEMI) or Non-ST Elevation Myocardial Infarction (non-STEMI). At Visit 1, after signing informed consent, study measurements will take place at days 1, 2, 3 and 5 post ACS, where feasible. It is planned that approximately 138 CAD patients will be randomized to ensure at least 66 evaluable patients receiving AZD5718 Dose B or placebo are included with 12 weeks treatment. For supporting dose selection in future studies, a treatment arm with 28 randomized patients receiving AZD5718 Dose A is included in the study. The study was originally designed to be a 4-week study and was amended to be a 12-week study. Therefore, the total number of patients is greater than required for a 12 weeks study (about 100), since some patients will only have 4 weeks of treatment.
An evaluable patient is defined as a patient with a valid Coronary Flow Velocity Reserve (CFVR) measurement at Visit 2 and one post baseline visit as judged by the CFVR Core lab.
On Day 1 (Visit 2), 7 to 28 days after the ACS event, patients willing to participate in the study will complete the screening procedure and, if eligible, be randomized. Treatment duration will be 12 weeks. During the treatment phase, patients will come in to the clinic for study measurements at 2 weeks (visit 3), 4 weeks (visit 4), 8 weeks (visit 4b) and 12 weeks (visit 4c).
A follow-up visit (Visit 5) will be performed at 4 weeks (±4 days) after last dose in order to ensure safety and well-being of the patients
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females of non-childbearing potential
- •Age ≥18 to ≤75
- •Body Mass Index (BMI) ≥18 to ≤35 kg/m2
- •CAD patients, here defined as:
- •ACS 7-28 days prior to study randomization (ACS defined as STEMI, non STEMI event documented by Electrocardiogram (ECG), cardiac enzymes [troponin] and angiogram) Provision of signed and dated, written informed consent prior to any study specific procedures
排除标准
- •Uncontrolled Type 1 or Type 2 diabetes defined as haemoglobin A1c (HbA1c) Diabetes
- •Control and Complications Trial (DCCT)> 9% or International Federation of Clinical Chemistry (IFCC) >74.9 mmol/mol
- •Patients with atrial fibrillation (chronic or current) or history of ventricular tachycardia requiring therapy for termination, or symptomatic sustained ventricular tachycardia or sick sinus syndrome or Atrioventricular blockage degree 2-3
- •Prior coronary artery by-pass graft (Coronary artery bypass grafting) to Left Anterior Descending artery (LAD)
- •Left ventricle ejection fraction < 30%
- •Unacceptable level of angina despite maximal medical therapy or unstable angina at entry
- •Canadian Cardiovascular Society (CCS) ≥ 3 (Visit 1 or Visit 2)
- •Stroke within the previous 6 months from ACS or ongoing treatment with Persantin or Asasantin
- •Chronic use of anticoagulants on therapeutic dose (not including thrombosis prophylaxis) during the study
- •Planned additional cardiac intervention (e.g., Percutaneous coronary intervention (PCI), Coronary artery bypass grafting (CABG) within next 6 months
- •New York Heart Association (NYHA) class III-IV heart failure or decompensated heart failure at discharge or hospitalization for exacerbation of chronic heart failure within the previous 3 months from ACS
- •Previously known severe renal disease (Chronic Kidney Disease (CKD) stage 4 or 5) or previously known creatinine clearance calculated by Cockcroft Gault equation <30 ml/min*m2
- •Known allergy to adenosine and mannitol, or experience of previous adverse effects of adenosine stress testing.
- •Participation in another interventional clinical study with an investigational pharmaceutical product during the last 3 months also including drug eluting stents.
研究组 & 干预措施
AZD5718 Dose A
AZD5718 Dose A once daily
干预措施: AZD5718 (Drug)
AZD5718 Dose B
AZD5718 Dose B once daily
干预措施: AZD5718 (Drug)
Placebo
Matching placebo once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Creatinine-normalized u-LTE4 at Week 4
时间窗: Baseline and 4 weeks
Creatinine-normalized u-LTE4 is calculated as uLTE4/creatinine
次要结局
- Summary of Plasma Concentrations of AZD5718(16 weeks)
- Change From Baseline in Creatinine-normalized u-LTE4 at Week 12(Baseline and 12 weeks)
- Change From Baseline in CFVR at Week 12(Baseline and 12 weeks)
- Change From Baseline in CFVR at Week 4(Baseline and 4 weeks)
- Change From Baseline in LAD Hypereamic Flow at 4 Weeks(Baseline and 4 weeks)
- Change From Baseline in LVEF at 4 Weeks(Baseline and 4 weeks)
- Change From Baseline in LV Longitudinal Early Diastolic Strain Rate at 4 Weeks(Baseline and 4 weeks)
- Change From Baseline in LV-GLS at Rest at Week 4(Baseline and 4 weeks)
- Change From Baseline in LV-GCS at Rest at Week 4(Baseline and 4 weeks)
- Change From Baseline in LAD Resting Mean Diastolic Flow Velocity at 4 Weeks(Baseline and 4 weeks)