Investigating the effects of dapagliflozin and balcinrenone on kidney function in older adults

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.

This study is testing if the medications dapagliflozin and balcinrenone can improve kidney function and overall health in older adults with stage 3 chronic kidney disease.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Klinikum Nürnberg (other)
• Drugs / interventions: immunotherapy
• Locations: 2 sites (Marseille and 1 other locations)
• Trial ID: NCT05884866 on ClinicalTrials.gov

What this trial studies

This study aims to explore how dapagliflozin, both alone and in combination with balcinrenone, affects body fluid and electrolyte balance, as well as energy metabolism in participants over 50 years old with stage 3 chronic kidney disease. Participants will be randomly assigned to one of four treatment groups and will receive daily oral doses for 28 days, alongside their current therapy. The study will take place at two sites, with specific analyses conducted to assess metabolic changes and safety throughout the intervention period.

Who should consider this trial

Good fit: Ideal candidates are individuals over 50 years old diagnosed with stage 3 chronic kidney disease and specific electrolyte levels.

Not a fit: Patients with severe chronic kidney disease or those with contraindications to the study medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management of fluid and electrolyte balance in patients with chronic kidney disease.

How similar studies have performed: Other studies have shown promise with SGLT2 inhibitors in managing chronic kidney disease, suggesting potential for success in this approach.

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

Where this trial is running

Marseille and 1 other locations

• Assistance Publique-Hopitaux de Marseille (AP-HM) — Marseille, France (TERMINATED)
• Klinikum Nuernberg — Nuremberg, Bavaria, Germany (RECRUITING)

Study contacts

• Principal investigator: Adriana Marton, MD — Klinikum Nuernberg
• Study coordinator: Adriana Marton, MD

Conditions: Chronic Renal Failure, Mechanistic Effects of SGLT2 Inhibition and/ or MR Antagonism on Body Fluid and Electrolyte Homeostatis, Chronic Kidney Disease Stage 3, Electrolyte and Fluid Balance Conditions, Chronic kidney disease, Water conservation, SGLT2 inhibitors, dapagliflozin, MR antagonists, balcinrenone