Comparison of BI 690517 and Spironolactone on Renal Hemodynamics and Protein Profiles in Patients with Heart Failure or Cardiovascular Disease and Chronic Kidney Disease

The primary objective is to compare the effects of the aldosterone synthase inhibitor, vicadrostat, against the steroidal mineralocorticoid receptor antagonist, spironolactone, on changes in kidney function from baseline to 4 and 26 weeks in patients with heart failure, cardiovascular disease, or chronic kidney disease. 3: Therapy.

The secondary objectives include evaluating:

• Changes in renal hemodynamic measurements from baseline to 4 and 26 weeks.
• Alterations in urinary and plasma protein profiles from baseline to 4 and 26 weeks.
• Changes in serum and plasma concentrations of potassium, creatinine, neutrophil gelatinase-associated lipocalin, renin, angiotensin II, aldosterone, and kidney injury molecule-1 from baseline to 4 and 26 weeks.
• Changes in the urinary albumin-to-creatinine ratio and urinary concentration of sodium, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 from baseline to 4 and 26 weeks.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients aged 18 years or older. Eligible individuals present with heart failure, cardiovascular disease, or chronic kidney disease. Specific requirements include an estimated glomerular filtration rate between 25 and 90 mL/min/1.73m², depending on the specific clinical profile and the presence of type 2 diabetes. Participants must have a serum potassium level of ≤ 5.0 mmol and be currently treated or eligible for background treatment with empagliflozin. Candidates must be outpatients on stable doses of other guideline-directed medical therapies for at least 4 weeks and must not have utilized a mineralocorticoid receptor antagonist or an aldosterone synthase inhibitor within the 6 months prior to enrollment.

This Phase 2 clinical trial is designed as a comparative study to evaluate the effects of the aldosterone synthase inhibitor, vicadrostat, against the steroidal mineralocorticoid receptor antagonist, spironolactone, on kidney function and renal hemodynamics. The study involves patients diagnosed with heart failure, cardiovascular disease, or chronic kidney disease. The primary objective is to assess changes in the estimated glomerular filtration rate from baseline to 4 and 26 weeks of treatment. Secondary endpoints include the evaluation of renal hemodynamic changes, such as effective renal plasma flow, renal blood flow, and renal vascular resistance, alongside assessments of plasma and urinary protein profiles and changes in the urine albumin-to-creatinine ratio. The research methodology involves a sequence of visits beginning with a screening phase to confirm eligibility based on criteria such as serum potassium levels and estimated glomerular filtration rate ranges. Following enrollment, participants undergo treatment monitoring at 4 weeks and a final assessment at 26 weeks. The total duration of participant involvement is determined by the 26-week treatment period. Background therapies may include empagliflozin, while iohexol and aminohippuric acid are utilized as auxiliary substances for hemodynamic measurements.

The investigational product is BI 690517, administered as a 10 mg film-coated tablet via the oral route.

The comparator treatment consists of spironolactone, provided in a 50 mg film-coated tablet for oral administration.

Background therapies include empagliflozin, administered as 10 mg film-coated tablets orally, and iohexol, administered as a 36 mg/kg solution for injection via infusion. Additionally, aminohippuric acid is utilized via infusion at a dose of 6 mg/kg.

The efficacy of vicadrostat compared to spironolactone is evaluated by assessing changes in kidney function. The primary endpoint is the change in the estimated glomerular filtration rate (eGFR) from baseline to 4 and 26 weeks of treatment.

Secondary endpoints include the assessment of renal hemodynamic changes. These parameters are measured at baseline, 4 weeks, and 26 weeks, and consist of:

• measured glomerular filtration rate (mGFR)
• effective renal plasma flow (ERPF)
• renal blood flow (RBF)
• renal vascular resistance (RVR)
• glomerular pressure (Pglo)
• afferent vascular resistance (Ra)
• efferent vascular resistance (Re)