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.

The Nuremberg site will perform metabolomics analyses and evaluation of metabolic longevity switches in erythrocytes; participants will be randomly allocated to 1 of the 4 treatment arms, with n=25 participants per arm. All participants in Nuremberg will undergo 3 study visits: at baseline, day 3 (to study the early effect of the intervention) and at day 28 (for the late metabolic effects). An additional safety study visit will take place at day 7+/-1. A follow-up visit will take place at day 28 +/- 7 after the last dose. Study procedures: medical examination, height, weight, blood pressure (BP), heart rate (HR), 24h urine collection and analysis, venous blood sampling. This site will prepare venous blood samples for metabolomic analysis and will perform the erythrocyte isolation protocol for the assessment of erythrocyte metabolism. The Marseille site will conduct an imaging sub-study to evaluate tissue sodium and water content, and muscle energy metabolism before and after the study intervention; participants will be randomly allocated to 1 of the 4 treatment arms, with n=10 participants per arm. All participants in Marseille will undergo 2 study visits: at baseline (before starting the intervention) and after 28 days of treatment. An additional safety study visit will take place at day 7+/-1. A follow-up visit will take place at day 28 +/- 7 after the last dose. Study procedures: medical examination, height, weight, blood pressure, heart rate, 24h urine collection and analysis, venous blood sampling, MRI scans. During each of the study visits at baseline and day 28 the participants will undergo 2 MRI scans: a 23Na MRI scan for the assessment of tissue sodium storage and water content at ultra-high field (7T MRI) and a spectroscopy scan for the assessment of muscle energy metabolism (phosphorus spectroscopy at 3T). The total duration of the scans at each study visit will be approximately 2h. The Marseille recruitment site has been closed in October 2024 because of low recruitment rate. The recruitment will be completed in Nuremberg, and the number of patients has been increased to 25 patients per arm. Considering the very low drop-out rate in Nuremberg (2%) a total of 100 participants (25 per arm) will be randomized into the study. This number will suffice to achieve the necessary sample size of 23 patients for arm, and meet the necessary sample size for the primary endpoint according to the initial statistical power calculation : 23 per arm, accounting for a drop-out rate of 8%. Enrolled means participants' or their legally acceptable representatives' agreement to participate in a clinical study following completion of the informed consent process. Potential participants who are screened for the purpose of determining eligibility for the study, but do not participate in the study, are not considered enrolled, unless otherwise specified by the protocol. A participant will be considered enrolled if the informed consent is not withdrawn prior to participating in any study activity after screening. Participants in this study will be randomized into one of the 4 treatment arms: 1. Balcinrenone 150 mg (n=30) 2. Balcinrenone 150 mg + Dapagliflozin 10 mg (n=30) 3. Dapagliflozin 10 mg (n=30) 4. Placebo (n=30) For each group, 25 participants per group will complete the study (total n=100). No dose modification, neither for dapagliflozin nor for balcinrenone, is planned during this study. To ensure a dose interval of about 24 hours, the medication should be taken every day in the morning. If a dose is missed by more than 12 hours, that dose should be skipped and the next dose should be taken as scheduled. No double doses should be taken. Because of the short treatment duration in this study (28 days) no temporary discontinuation can take place, as this can affect the metabolic phenotype at day 3 and day 28. Therefore, if a participant needs to discontinue the study intervention, this participant will be withdrawn from the study and replaced. Treatment duration will be 28 days, up to a maximum of 32 days to allow for scheduling flexibility. A follow-up visit will take place approximately one month (28 days +/-7 days) after the end of the intervention period. The screening visit may take place anytime within 4 weeks prior to Baseline visit. Therefore, the estimated total study duration for each participant, including screening and follow-up is 2 to 3 months.