A Study to Investigate the Mechanistic Effects of Dapagliflozin Alone or in Combination With Balcinrenone, Compared to Balcinrenone and Placebo on Body Fluid and Electrolyte Handling and Energy Metabolism in Participants Over 50 Years of Age With Chronic Kidney Disease. (DapaBalci-Leap)
Chronic Renal Failure, Mechanistic Effects of SGLT2 Inhibition and/ or MR Antagonism on Body Fluid and Electrolyte Homeostatis
About this trial
This is an interventional treatment trial for Chronic Renal Failure focused on measuring Chronic kidney disease, Water conservation, SGLT2 inhibitors, dapagliflozin, MR antagonists, balcinrenone, Amino acids, Energy metabolism
Eligibility Criteria
Inclusion Criteria: Diagnosis of chronic kidney disease, with eGFR ≥30 and ≤60 mL/min/1.73m2 Serum/ plasma K+ levels ≥ 3.5 and < 5.0 mmol/L within 2 weeks prior to randomization Serum/plasma Na+ levels within normal reference values within 2 weeks prior to randomization If participants have type 2 diabetes mellitus, treatment with metformin, sulphonylureas, DPP4 inhibitors or any combinations of these agents with or without insulin would be accepted but is not mandatory. If used, stable dose of metformin, sulphonylureas, or DPP4 inhibitors or their combination as anti-diabetic therapy for the 12 weeks prior to randomization is required No changes in background treatment for at least 3 weeks prior to randomization Body mass index less than 40 kg/m2 Negative pregnancy test (urine or serum) for female subjects of childbearing potential and willingness to use a highly effective birth control (see Appendix 4) if of childbearing potential. Willingness to participate and ability to provide signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Exclusion Criteria: Diagnosis of type 1 diabetes mellitus Uncontrolled type 2 diabetes mellitus with HbA1C > 10.5% in the most recent medical records Participants with type 2 diabetes mellitus treated with insulin if insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) was not stable in the 12 weeks prior to randomization as judged by the Investigator Patients with systolic blood pressure levels <100 mmHg at the time of enrolment Patients with congestive heart failure NYHA stage IV or hospitalized for decompensation of heart failure in the 3 months prior to screening History of any life-threatening cardiac arrhythmias, or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter 7. Acute coronary syndrome and/or percutaneous cardiac interventions within 3 months prior to screening Unstable or rapidly progressing renal disease Chronic cystitis and recurrent genital or urinary tract infections Significant hepatic disease, including hepatitis and/or liver cirrhosis (Child-Pugh class A-C), or AST or ALT > 2 × ULN (upper limit of normal); or total bilirubin levels (TBL) > 2 × ULN; or serum albumin levels < 3.5 g/dL Medical conditions associated with development of hyperkalemia (Addison's disease) Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within 3 months prior to screening Hemoglobin levels below 8.5 g/dL or over 15 g/dL Patients who have received an organ or bone marrow transplant HIV infection Active cancer, history of bladder cancer Patients who have had major surgery in the 3 months prior to screening Patients with muscular dystrophies Patients who have severe comorbid conditions likely to compromise survival or study participation Pregnant and breast-feeding women
Sites / Locations
- Assistance Publique-Hopitaux de Marseille (AP-HM)
- Klinikum NuernbergRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Experimental
Placebo Comparator
Dapagliflozin
Balcinrenone
Dapagliflozin + Balcinrenone
Placebo
1 tablet Dapagliflozin 10 mg + 1 capsule Balcinrenone 50mg matching Placebo + 1 capsule Balcinrenone 100 mg matching Placebo
1 capsule Balcinrenone 50mg + 1 capsule Balcinrenone 100 mg + 1 tablet Dapagliflozin matching Placebo
1 tablet Dapagliflozin 10mg + 1 capsule Balcinrenone 50mg + 1 capsule Balcinrenone 100 mg
1 tablet Dapagliflozin matching Placebo + 1 capsule Balcinrenone 50mg matching Placebo + 1 capsule Balcinrenone 100 mg matching Placebo