A Phase Ib Study of AZD5462 on Top of Dapagliflozin in Participants With Heart Failure and Moderate Renal Impairment (AURORA)

AstraZeneca

Status and phase: Terminated; Phase 1

Conditions: Renal Impairment; Heart Failure

Treatments: Drug: AZD5462; Other: Placebo; Drug: Dapagliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06639087

2024-513142-11-00 (Registry Identifier)

D9090C00007

Details and patient eligibility

About

A study to investigate the effects and safety of AZD5462 on top of dapagliflozin in participants with heart failure and moderate renal impairment.

Full 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)

Enrollment: 8 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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8 participants in 2 patient groups, including a placebo group

AZD5462 + dapagliflozin

Active Comparator group

Description:

Participants will receive AZD5462 on top of dapagliflozin once daily.

Treatment:

Drug: Dapagliflozin

Drug: AZD5462

Placebo + dapagliflozin

Placebo Comparator group

Description:

Participants will receive placebo on top of dapagliflozin once daily.

Treatment:

Other: Placebo

Drug: Dapagliflozin