Phase 2
Completed N=153
Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease
Source: ClinicalTrials.gov NCT04595370 ↗Enrolled (actual)
153
Serious AEs
8.5%
Results posted
Nov 2024
Primary outcomePrimary: Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 — -56.391; -42.085; -58.047; -45.01 Percent change from baseline — p=0.3645
Summary
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]).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12 |
-56.391; -42.085; -58.047; -45.01; -34.318; 230.32 | 0.3645 |
| SECONDARY Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at 12 Weeks to Assess Dose-Response Relationship |
-56.391; -42.085; -58.047; -45.01; -34.318; 230.32 | 0.1588 |
| SECONDARY Number of Participants With Adverse Events (AEs) |
9; 12; 18; 5; 14; 3 | — |
| SECONDARY Change From Baseline in Serum Potassium (K+) |
0.056; 0.003; 0.109; 0.55; 0.040; 0.03 | — |
| SECONDARY Absolute Value of Serum Potassium Over Time |
4.60; 4.44; 4.46; 4.50; 4.60; 4.50 | — |
| SECONDARY Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) |
-1.432; -1.160; -5.307; -0.923; -3.498; 6.880 | — |
| SECONDARY Absolute Value of eGFR Over Time |
41.341; 38.586; 43.663; 36.874; 41.895; 40.288 | — |
Eligibility Criteria
Inclusion Criteria
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 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
Data sourced from ClinicalTrials.gov (NCT04595370). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.