Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease

Completed · Phase 2

Conditions studied: Heart Failure, Chronic Kidney Disease

In brief

The purpose of the study is to evaluate the efficacy and safety of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone and to assess the dose-response relationship, dapagliflozin alone and 3 doses of AZD9977 combined with dapagliflozin on urinary albumin to creatinine ratio (UACR). The study will be conducted in participants with heart failure (HF) with left ventricular ejection fraction (LVEF \[below 60%\]) and chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR \[between ≥ 20 and ≤ 60 mL/min/1.73 m\^2, with at least 20% of participants with eGFR ≥ 20 to \<30 mL/min/1.73\^2 and a maximum of 35% of participants with eGFR ≥ 45 mL/min/1.73 m\^2\]).

Key facts

Study ID: NCT04595370
Run by: AstraZeneca
People needed: 153
Starts: 2021-01-26
Expected to finish: 2023-09-22
Last updated by the study team: 2024-11-19

Who can join

Age: 21 and older, up to 130. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Participants are included in the study if any of the following criteria apply:
Documented diagnosis of stable symptomatic HF (New York Heart Association class II-III) at screening, and a medical history of typical symptoms and signs of HF in those who are currently receiving loop diuretic treatment
Left ventricular ejection fraction <60% documented by the most recent echocardiogram or cardiac magnetic resonance imaging within the last 12 months prior to screening
Stable background treatment for HF, hypertension, diabetes mellitus or renal disease according to guidelines
N-terminal-pro-brain natriuretic peptide (NT proBNP) ≥300 pg/mL for participants with sinus rhythm at screening; and NT proBNP ≥600 pg/mL for participants with atrial fibrillation/flutter at screening
The eGFR ≥30 and ≤60 mL/min/1.73\^2 (by CKD- EPI formula) and UACR ≥30 mg/g (3 mg/mmol) and <3000 mg/g (300 mg/mmol)
Body mass index less than 40 kg/m\^2
Serum/plasma K+ level ≥ 3.5 and < 5.0 mmol/L within 10 days prior to randomization
Serum/ plasma Na+ level within normal reference values within 10 days prior to randomization
Systolic blood pressure should be at protocol defined range at randomization (Visit 3), with no change to antihypertensive treatments in previous 3 weeks
Male or female of non-childbearing potential
All participants must follow protocol defined contraceptives procedures

You may not qualify if…

Participants are excluded from the study if any of the following criteria apply:
Primary glomerulopathy, vasculitic renal disease, prior dialysis or unstable rapidly progressing renal disease, autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasm antibody-associated vasculitis
Participants with currently decompensated HF requiring hospitalization for optimization of HF treatment and are not on stable HF therapy at the time of enrollment
HF due to cardiomyopathies
High output HF (e.g., due to hyperthyroidism or Paget's disease)
HF due to pericardial disease, congenital heart disease or clinically significant uncorrected primary cardiac valvular disease or planned cardiac valve repair/replacement
Participants with uncontrolled diabetes mellitus (Glycated hemoglobin >10%)
Participants with Type 1 diabetes mellitus
Intermittent or persistent 2nd or 3rd degree atrioventricular block, sinus node dysfunction with clinically significant bradycardia or sinus pauses, not treated with a pacemaker
History of any life-threatening cardiac dysrhythmia or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter
Acute coronary syndrome and/or elective/non-elective percutaneous cardiac interventions (within 3 months) prior to randomisation or is planned to undergo any of these procedures during the study
Any major cardiovascular (eg, open chest, coronary artery bypass grafting or valvular repair/replacement) or major non-cardiovascular surgery within 3 months prior to randomisation or is planned to undergo any cardiovascular surgery during the study
Heart transplantation or left ventricular assist device at any time or if these are planned
Kidney or any organ transplantation or if these are planned
Medical conditions associated with development of hyperkalaemia (Addison's disease )
History or ongoing allergy/hypersensitivity, to sodium-glucose co-transporter-2 inhibitor (SGLT2i e.g., dapagliflozin, empagliflozin)
Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within previous 3 months prior to randomisation
Hepatic disease, including hepatitis and/or hepatic impairment (Child-Pugh class A-C), and aspartate aminotransferase or alanine transaminase or total bilirubin should be in protocol defined range at time of screening and/ or within 7 days prior to randomization
Participants with newly detected pathological laboratory values or an ongoing disease condition
If the participants clinical signs and symptoms consistent with COVID-19, and has been previously hospitalized with COVID-19 infection and did not fully recover their previous health status
Previous randomization in the present study
Prior medical treatment with an mineralocorticoid receptor antagonist where the medication was taken within 90 days prior to screening
Current or prior treatment within 6 months prior to screening with cytotoxic therapy, immunosuppressive therapy, or other immunotherapy

Where it is running

Research Site — Fountain Valley, California, United States
Research Site — Northridge, California, United States
Research Site — South Gate, California, United States
Research Site — Hialeah, Florida, United States
Research Site — Homestead, Florida, United States
Research Site — Jacksonville, Florida, United States
Research Site — Miami, Florida, United States
Research Site — Ocala, Florida, United States
Research Site — Tampa, Florida, United States
Research Site — Augusta, Georgia, United States
Research Site — Columbus, Georgia, United States
Research Site — Baltimore, Maryland, United States
Research Site — Methuen, Massachusetts, United States
Research Site — St Louis, Missouri, United States
Research Site — The Bronx, New York, United States
Research Site — New Bern, North Carolina, United States
Research Site — Rapid City, South Dakota, United States
Research Site — Memphis, Tennessee, United States
Research Site — Houston, Texas, United States
Research Site — Houston, Texas, United States
Research Site — Kingwood, Texas, United States
Research Site — McKinney, Texas, United States
Research Site — San Antonio, Texas, United States
Research Site — Sherman, Texas, United States
Research Site — Beverly Hills, California, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.