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

Phase 1

Recruiting

• Conditions: Renal Impairment; Heart Failure
• Interventions: Drug: AZD5462; Drug: Dapagliflozin; Other: Placebo

• Registration Number: NCT06639087
• Lead Sponsor: AstraZeneca

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:
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-09-13
• Study Start: 2024-09-27
• Status Verified: 2024-10
• Study First Submitted QC: 2024-10-11
• Last Update Submitted: 2024-10-11
• Study First Posted: 2024-10-14
• Last Update Posted: 2024-10-14
• Primary Completion: 2025-09-08
• Study Completion: 2025-09-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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 6 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.

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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, ablation of atrial fibrillation/flutter, 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AZD5462 + dapagliflozin	AZD5462	Participants will receive AZD5462 on top of dapagliflozin once daily.
AZD5462 + dapagliflozin	Dapagliflozin	Participants will receive AZD5462 on top of dapagliflozin once daily.
Placebo + dapagliflozin	Dapagliflozin	Participants will receive placebo on top of dapagliflozin once daily.
Placebo + dapagliflozin	Placebo	Participants will receive placebo on top of dapagliflozin once daily.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (1)

Research Site; 🇸🇪 Mölndal, Sweden