A Phase 1b Randomized Clinical Trial of AZD5642 and Dapagliflozin in Patients With Heart Failure and Moderate Renal Impairment

Abstract

AZD5462 is the first oral selective relaxin/insulin-like family peptide receptor 1 agonist in clinical development. The aim of this mechanistic study is to investigate the renal effects of AZD5462 when administered on top of the sodium–glucose cotransporter 2 inhibitor dapagliflozin in participants with heart failure and moderate renal impairment. AURORA is a phase 1b, placebo-controlled, double-blind, 2-centre study of AZD5462 on top of dapagliflozin as standard of care in 2 arms. Approximately 40 participants with heart failure with ejection fraction ≤50% and moderate renal impairment (estimated glomerular filtration rate of 30–60 mL/min/1.73 m², inclusive) will be randomized 1:1 to AZD5462 or placebo tablets for a treatment period of 4 weeks. All participants will be standardized to 10 mg dapagliflozin prior to AZD5462 administration, and dapagliflozin as standard of care will continue until the end of the follow-up period. The objectives of the study are to evaluate the renal and haemodynamic effects of AZD5462 compared with placebo on top of dapagliflozin on natriuresis, albuminuria, haematocrit, fluid balance, cardiorenal biomarkers, and systemic hemodynamics. The safety and tolerability of AZD5462 will be further evaluated compared with placebo on top of dapagliflozin. AURORA is a phase 1b pharmacodynamic, pharmacokinetic, and safety study of AZD5462 on top of dapagliflozin in patients with heart failure and renal impairment.