The main purpose of this study is to evaluate the effect of AZD5462 on cardiac function in participants with chronic heart failure (HF).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
375
Cohort A and B: Change from Baseline in Echocardiography Parameters
To evaluate the effect of AZD5462 after treatment in participants with HF.
Time frame: From Baseline to Week 25
Cohort A and B: Change from Baseline in Echocardiography Parameters
To evaluate the effect and dose response of AZD5462 and effect on echocardiographic markers related to structural, systolic and diastolic function after treatment in participants with HF.
Time frame: 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)
To evaluate the effect of AZD5462 on HF health status in participants with HF. The KCCQ is a validated questionnaire developed for patients with congestive HF. It is a 23-item, self-administered health status measure that quantifies physical limitations, symptoms, social interference, self-efficacy, and quality of life. Results for each domain are summarized and transformed to a score of 0 to 100 with higher scores indicating better health status.
Time frame: 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)
To evaluate the effect of AZD5462 on HF health status in participants with HF. The NYHA Functional Classification is a system to measure the severity of symptoms of heart failure. It places patients in four categories based on limitations of physical activity, from Class I with no limitation, progressing to Class IV with severe limitations.
Time frame: Baseline and Week 25
Cohorts A and B: Change from Baseline in cardiac biomarkers
To evaluate the effect of AZD5462 on biomarkers of cardiac function in treatment participants with HF.
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Research Site
Alexander City, Alabama, United States
Research Site
Northridge, California, United States
Research Site
Torrance, California, United States
Research Site
Vista, California, United States
Research Site
Miami, Florida, United States
Research Site
Miami Beach, Florida, United States
Research Site
Richmond, Indiana, United States
Research Site
Boston, Massachusetts, United States
Research Site
Buffalo, New York, United States
Research Site
Rosedale, New York, United States
...and 47 more locations
Time frame: From Baseline to Weeks 5, 13, and 25
Cohorts A and B : Plasma Concentration of AZD5462
To evaluate the PK of AZD5462 after repeat OD oral dosing in participants with HF.
Time frame: 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)
To evaluate the safety and tolerability of AZD5462 as compared to placebo in participants with HF.
Time frame: From Baseline to Week 29 (Day 197)