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.

Launched by KLINIKUM NÜRNBERG · May 23, 2023

Keywords

ClinConnect Summary

This clinical trial is studying the effects of two medications, dapagliflozin and balcinrenone, on how the body manages water and electrolytes, as well as energy use, in people over 50 with chronic kidney disease. Participants will take the medications daily for 28 days, alongside their usual treatments. The goal is to see how these drugs can help improve kidney function and overall health by analyzing urine and blood samples. The study is taking place at two locations, with one site focusing on how the medications affect metabolism and the other looking at changes in body tissues.

To be eligible for the trial, participants must be diagnosed with chronic kidney disease and have certain kidney function test results. They should also have stable blood pressure and not be using specific medications or have certain medical conditions that could interfere with the study. Participants will need to provide informed consent and will receive close monitoring throughout the trial. This study is an important step in understanding how these medications work and could lead to better treatments for chronic kidney disease in the future.

Gender

ALL

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 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.
• 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
• • 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 OR over the normal laboratory ranges, when these are provided
• • Patients who have received an organ transplant at any time or bone marrow transplant in the previous 10 years
• • 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
• • Medical treatment with either a mineralocorticoid receptor antagonist (MRA) or a sodium-glucose co-transporter-2 inhibitor (SGLT2i) within 3 months prior to screening
• • Medical treatment with potassium binders
• • Medical treatment with strong or moderate CYP3A4 inducers or inhibitors
• • Prior serious hypersensitivity reaction to dapagliflozin (Forxiga®), balcinrenone or to any of their excipients
• • Treatment with cytotoxic therapy, immunosuppressive therapy or other immunotherapy within 6 months prior to screening
• • Unwillingness or other inability to cooperate
• • For patients undergoing MRI scans, presence of implanted devices (surgical clips, heart pacemakers or defibrillators, cochlear implants), iron-based tattoos, any other pieces of metal or devices that are not MR-safe anywhere in the body