Renal Impairment, Heart Failure
Conditions
Keywords
Relaxin family peptide receptor 1 agonist, Estimated glomerular filtration rate, Heart failure, Renal impairment
Brief summary
A study to investigate the effects and safety of AZD5462 on top of dapagliflozin in participants with heart failure and moderate renal impairment.
Detailed description
This is a randomized, double-blind, placebo-controlled Phase 1b study to evaluate the safety, pharmacodynamics, and pharmacokinetics of AZD5462 on top of dapagliflozin in participants with heart failure and renal impairment. The study will include 5 periods and approximately 9 study site visits: * Screening Period of up to 4 weeks (at least one study visit) * Run-in Period of up to 4 weeks (one study visit) * Inpatient Treatment Period of 4 days (one study visit) * Outpatient Treatment Period of up to 4 weeks (three study visits) * Follow-up Period of up to 4 weeks (three study visits)
Interventions
DRUGAZD5462
Participants will receive AZD5462 on top of dapagliflozin once daily.
DRUGDapagliflozin
Participants will receive dapagliflozin once daily with AZD5462 or placebo.
OTHERPlacebo
Participants will receive placebo on top of dapagliflozin once daily.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have a pre-existing diagnosis of heart failure (HF). * Participants must have a left ventricular ejection fraction (LVEF) of ≤ 40% based on echocardiography taken within the last 9 months. * Participants must have an estimated glomerular filtration rate (eGFR) of 30 to 60 milliliters per minute per 1.73 meters squared (mL/min/1.73 m2) (inclusive) at Screening as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 (creatinine) equation. * Participants must be on stable HF standard of care (SoC) medication for at least 4 weeks prior to Screening. If the participant is currently taking diuretics, then diuretics must also be stable for at least one week prior to Screening. * Participants must be on stable Sodium-glucose co-transporter-2 inhibitors (SGLT2) inhibitor treatment for at least 12 weeks prior to Screening. * Minimum BMI of 18 kilograms per meter squared (kg/m2) at Screening.
Exclusion criteria
* Historical or current evidence of a clinically significant disease or disorder. * Participants with a known hypersensitivity to AZD5462 or dapagliflozin, or to any of the excipients of these drug products. * Congenital long QT syndrome or history of QT prolongation associated with other medications that required discontinuation of that medication. * Cardiac ventricular arrhythmia that requires treatment. However, participants with atrial fibrillation or flutter and controlled ventricular rate (eg, resting heart rate \< 110 beats per minute) are permitted. Participants with cardiac ventricular arrhythmia that are treated with antiarrhythmic agents (eg, amiodarone) and are stable are permitted. * History of or anticipated heart transplant. * Any planned highly invasive cardiovascular procedure (eg, coronary revascularisation, valve repair/replacement, aortic aneurysm surgery). * Any evidence of clinically important disease or disorder which in the Investigator's opinion makes it undesirable for the participant to participate in the study. * Positive hepatitis C antibody, hepatitis B virus surface antigen, or hepatitis B virus core antibody at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in sodium excretion | From Baseline to Day 1 | To evaluate the effect of AZD5462 on top of dapagliflozin in participants with heart failure (HF) and renal impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in urine albumin-creatinine ratio (uACR) | From Baseline to Day 1 and 29 | To evaluate the effect of AZD5462 on top of dapagliflozin in participants with HF and renal impairment. |
| Change in haematocrit | From Baseline to Day 29 | To evaluate the effect of AZD5462 on top of dapagliflozin in participants with HF and renal impairment. |
| Number of adverse events (AEs) and Serious Adverse Events (SAEs) | From Baseline to Day 57 | To evaluate the effect of AZD5462 on top of dapagliflozin in participants with HF and renal impairment. |
Countries
Bulgaria
Outcome results
None listed