Natriuretic-ureothelic Adaptation of Body Fluid Homeostasis During SGLT-2 Inhibition and/or Mineralocorticoid Receptor Modulation in Patients With Chronic Kidney Disease. A 4-arm, Double-blind, Double-dummy, Parallel-group, Phase 2 Study to Investigate the Mechanistic Effects of Dapagliflozin, Dapagliflozin + Balcinrenone, Balcinrenone and Placebo on Body Solute and Water Homeostasis and Energy Metabolism in Male and Female Participants Over 50 Years of Age With Chronic Kidney Disease.
The purpose of this study is to investigate the mechanistic effects of dapagliflozin 10 mg, alone or in combination with balcinrenone 150 mg, with balcinrenone 150 mg and placebo, on the way the body handles electrolytes and water content, as well as the effects these interventions may have on energy metabolism in participants with stage 3 chronic kidney disease. The study interventions will be administered orally, daily, in addition to current therapy, for a duration of 28 days. This will allow us to maximize our ability to detect a drug effect while minimizing the drop-out rate that accompanies longer studies. In order to understand the different mechanistic effects of these interventions on energy metabolism, the study will be conducted at two study sites. The study design and treatment allocation, treatment duration as well as sample analysis for evaluation of the primary endpoint will be identical for all participants, at both sites. Therefore, urine and plasma samples for analysis of water and electrolyte handling will be collected from all study participants at both sites. In addition to the primary endpoint, the main study site (Nuremberg) will conduct a metabolic study to investigate the early- and late-effects of the interventions, while the second site, Marseille, will conduct an imaging sub-study to assess changes at the tissue level before and after treatment.
• 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 OR within normal laboratory ranges when these are provided, 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.