A Phase IIb Two-Cohort, Randomised, Placebo-controlled, Double-blind, Multi-centre, Dose-ranging Study of AZD5462 in Stable Patients With Chronic Heart Failure
概览
- 阶段
- 2 期
- 干预措施
- AZD5462
- 疾病 / 适应症
- Chronic Heart Failure
- 发起方
- AstraZeneca
- 入组人数
- 375
- 试验地点
- 57
- 主要终点
- Cohort A and B: Change from Baseline in Echocardiography Parameters
- 状态
- 已完成
- 最后更新
- 2个月前
概览
简要总结
The main purpose of this study is to evaluate the effect of AZD5462 on cardiac function in participants with chronic heart failure (HF).
详细描述
This is a Phase IIb randomized, double-blind, placebo-controlled, multi-center, dose-ranging study to evaluate the efficacy, safety, and pharmacokinetic (PK) of AZD5462 on top of standard of care in 2 cohorts of participants with HF: Cohort A, and Cohort B. The study will include 3 periods and approximately 12 study visits: * Screening period of up to 4 weeks (at least 1 study visit) * Treatment period of 24 weeks (8 study visits) * Follow-up period of 4 weeks (3 study visits) Eligible participants in each cohort will be randomized equally 1:1:1:1 to receive a once daily dose (OD) of 3 dose levels (low, medium, or high) oral dose of AZD5462 tablets or placebo.
研究者
入排标准
入选标准
- •Participants must have a pre-existing diagnosis of HF NYHA FC II to IV.
- •Participants must be on stable HF standard of care medication for at least 4 weeks prior to consent and during the Screening period.
- •Minimum body mass index (BMI) of 18 kilograms per meter square (kg/m\^2) at Screening.
- •For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential.
- •All male participants should refrain from fathering a child or donating sperm until 3 months after the final study Follow-up Visit. Non-sterilised male participants should avoid fathering a child either by true abstinence or use of a condom for all sexual intercourse with a female partner of childbearing potential from the first dose until 3 months after the final Follow-up Visit.
排除标准
- •Historical or current evidence of a clinically significant disease or disorder including, but not limited to:
- •Myocardial infarction, stroke, transient ischaemic attack, coronary artery bypass grafting, or percutaneous coronary intervention within 12 weeks prior to consent or transcatheter structural heart interventions or cardiac valve surgery within 6 months prior to consent.
- •Sarcoidosis, restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, or hypertrophic (obstructive) cardiomyopathy.
- •History of untreated clinically significant valve disease or a Screening confirmation of severe aortic stenosis, severe mitral stenosis, moderate or severe aortic insufficiency or severe mitral insufficiency.
- •Amyloidosis, Fabry disease, or haemochromatosis.
- •Pericardial disease (i.e., visually significant white pericardium on echocardiogram).
- •Known coagulation disorders.
- •Current diagnosis of active hepatitis.
- •Severe pulmonary disease that is not expected to improve over time, as assessed by the investigator.
- •Decompensated HF or any cardiopulmonary hospitalisation, except planned hospitalisation without worsening of cardiac or pulmonary functions, within 4 weeks prior to consent or during the Screening period.
研究组 & 干预措施
Cohort A & B: AZD5462 low dose
Participants will receive low dose of AZD5462 as OD tablets for 24 weeks.
干预措施: AZD5462
Cohort A & B: AZD5462 medium dose
Participants will receive medium dose of AZD5462 as OD tablets for 24 weeks.
干预措施: AZD5462
Cohort A & B: AZD5462 high dose
Participants will receive high dose of AZD5462 as OD tablets for 24 weeks.
干预措施: AZD5462
Cohort A & B: Placebo
Participants will receive matching placebo OD tablets for 24 weeks.
干预措施: Placebo
结局指标
主要结局
Cohort A and B: Change from Baseline in Echocardiography Parameters
时间窗: From Baseline to Week 25
To evaluate the effect of AZD5462 after treatment in participants with HF.
次要结局
- Cohort A and B: Change from Baseline in Echocardiography Parameters(From Baseline to Week 13 and Week 25)
- Cohorts A and B: Change from Baseline in Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS)(From Baseline to Weeks 3, 5, 13, and 25)
- Cohorts A and B: Change from Baseline in New York Heart Association Functional Class (NYHA FC)(Baseline and Week 25)
- Cohorts A and B: Change from Baseline in cardiac biomarkers(From Baseline to Weeks 5, 13, and 25)
- Cohorts A and B : Plasma Concentration of AZD5462(Day 15 (Week 3), Day 29 (Week 5) and 85 (Week 13))
- Cohorts A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Baseline to Week 29 (Day 197))