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 Ch

• Status: Recruiting
• Trial end date: 2025-01-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Klinikum Nürnberg
• Treatments: Dapagliflozin

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