Informations générales (source: ClinicalTrials.gov)
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. (DapaBalci-Leap)
Interventional
Phase 2
Klinikum Nürnberg (Voir sur ClinicalTrials)
juillet 2023
juin 2026
08 mai 2025
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.
Etablissements
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Assistance Publique-Hopitaux de Marseille (AP-HM) - 13005 - Marseille - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
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.
- 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.
- 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