a phase ib study of azd5462 on top of dapagliflozin in participants with heart failure and moderate renal impairment

Conditions: Renal Impairment; Heart Failure

Summary: a study to investigate the effects and safety of azd5462 on top of dapagliflozin in participants with heart failure and moderate renal impairment.

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)

Eligibility criteria:
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.

Keywords: relaxin family peptide receptor 1 agonist estimated glomerular filtration rate heart failure renal impairment