Evaluation of Vicadrostat and Empagliflozin in Simultaneous vs. Staggered Initiation for Chronic Kidney Disease Progression Risk

The primary objective of this Phase II randomized, double-blind, parallel-group, multicenter, international trial is to evaluate the **safety** and **efficacy** of staggered versus simultaneous initiation of **vicadrostat** in combination with **empagliflozin** in participants with **chronic kidney disease**. The focus is on assessing the absolute change in estimated glomerular filtration rate (**eGFR**) from baseline to Week 14. This is clinically relevant as eGFR is a critical marker of kidney function, and improvements in eGFR can indicate a slowing of disease progression in chronic kidney disease.

Secondary objectives include comparing the two initiation strategies for their effects on absolute changes in systolic blood pressure (**SBP**) and serum potassium levels from baseline to Week 12, as well as the relative change in urine albumin creatinine ratio (**UACR**) from baseline to Week 6. These parameters are important as they provide additional insights into cardiovascular and renal outcomes, which are crucial for managing chronic kidney disease.

The clinical trial involves a total of **316 participants** diagnosed with **chronic kidney disease**. The study population includes both male and female subjects, aged 18 years and older, who have provided signed and dated written informed consent. Participants are required to have evidence of chronic kidney disease at risk of progression, as indicated by specific eGFR measurements. The trial population was selected based on their treatment with a stable dose of either ACE inhibitors or angiotensin receptor blockers for at least four weeks prior to the trial, with no planned changes in therapy during the study period. The participants are not part of a vulnerable population, and the trial does not impose specific lifestyle considerations such as diet or physical activity. Key inclusion criteria include the ability of women of childbearing potential to use highly effective methods of birth control, while men are not required to use birth control during the trial.

The clinical trial is a **Phase II**, randomized, double-blind, parallel-group, multicenter, international study designed to evaluate the safety and efficacy of **vicadrostat** and **empagliflozin** in participants with **chronic kidney disease** at risk of progression. The trial aims to compare the effects of staggered versus simultaneous initiation of these medications on the absolute change in estimated glomerular filtration rate (eGFR) from baseline to Week 14. The study will involve the administration of **BI 690517** and **Jardiance 10 mg film-coated tablets**, with a placebo matching **vicadrostat** also being utilized. The trial is expected to commence recruitment on July 1, 2025, and conclude by January 8, 2027.

Participants will be involved in the study for a maximum treatment period of 12 weeks. The trial will include several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be at least 18 years old, have evidence of chronic kidney disease with specific eGFR measurements, and be on a stable dose of either an ACE inhibitor or an angiotensin receptor blocker for at least four weeks prior to the first visit. Participants must also provide signed informed consent and, if applicable, adhere to specific birth control requirements.

The primary endpoint is the absolute change in eGFR from baseline to Week 14, with secondary endpoints including changes in eGFR and systolic blood pressure at Week 12, relative change in urine albumin-to-creatinine ratio at Week 6, and changes in serum potassium levels at Week 12. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial is not classified as low intervention and is conducted to investigate the safety and efficacy of the new therapy in patients with chronic kidney disease.

The clinical trial involves the administration of **BI 690517**, an experimental medication provided in the form of a **film-coated tablet**. The active substance, also named BI 690517, is of chemical origin. The medication is administered orally with a maximum daily dose of 10 mg and a total maximum dose of 840 mg over a treatment period of 12 weeks. The trial aims to evaluate the safety and efficacy of this compound in participants with chronic kidney disease at risk of progression.

In addition to the experimental medication, a **placebo** matching vicadrostat is utilized in the study. The placebo is designed to mimic the appearance of the active medication but does not contain any active pharmaceutical ingredients. It serves as a control to assess the efficacy of the experimental treatment by providing a baseline for comparison.

**Jardiance**, containing the active substance **empagliflozin**, is also included in the trial. This medication is provided as a 10 mg film-coated tablet and is administered orally. Similar to BI 690517, the maximum daily dose is 10 mg, with a total maximum dose of 840 mg over a 12-week period. Jardiance is a standard-of-care therapy used to manage chronic kidney disease and is included in the trial to compare its effects when initiated simultaneously or staggered with BI 690517.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The trial's primary objective is to compare the effects of staggered versus simultaneous initiation of vicadrostat in combination with empagliflozin on the absolute change in estimated glomerular filtration rate (eGFR) from baseline to Week 14.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the absolute change in estimated **glomerular filtration rate (eGFR)** from baseline to Week 14. This parameter will be measured to determine the effect of staggered versus simultaneous initiation of vicadrostat in combination with empagliflozin in participants with chronic kidney disease at risk of progression.

Secondary endpoints include the absolute change in eGFR from baseline to Week 12, absolute change in systolic blood pressure (SBP) from baseline to Week 12, relative change in urine albumin-to-creatinine ratio (UACR) from baseline to Week 6, and absolute change in serum potassium levels from baseline to Week 12. These parameters will be collected and analyzed at specified time points to provide a comprehensive assessment of the treatment's efficacy.