Evaluation of Vicadrostat (BI 690517) and Empagliflozin Efficacy and Safety in Type 2 Diabetes, Hypertension, and Cardiovascular Disease Patients

The primary objective is to evaluate the efficacy of combining vicadrostat and empagliflozin compared to vicadrostat plus placebo or empagliflozin monotherapy in patients presenting with type 2 diabetes, hypertension, and established cardiovascular disease. This assessment focuses on the time to the first occurrence of cardiovascular death, hospitalization for heart failure, or urgent heart failure visit. The study also aims to monitor safety outcomes within this patient population.

The study involves a total of 7224 participants, consisting of both males and females. The population includes individuals aged 18 years or older who have been diagnosed with type 2 diabetes, hypertension, and established cardiovascular disease. All participants must be receiving active pharmacological treatment for these conditions according to standard of care. Additionally, subjects must present at least one additional risk factor for developing heart failure. Participants of childbearing potential are required to utilize highly effective contraception methods. The trial population is selected based on these clinical requirements and the provision of written informed consent.

This Phase III, double-blind, randomised, parallel-group superiority trial is designed to evaluate the efficacy and safety of combining oral vicadrostat (BI 690517) and empagliflozin compared to placebo and empagliflozin. The study focuses on participants diagnosed with type 2 diabetes, hypertension, and established cardiovascular disease. The primary objective is to assess the time to the first occurrence of cardiovascular death or heart failure event, which includes hospitalisation for heart failure or an urgent heart failure visit. Secondary endpoints involve measuring changes in systolic blood pressure, urinary albumin-to-creatinine ratio, and the occurrence of major adverse cardiovascular events. The research methodology involves a comparative analysis between the test combination and the control groups to determine clinical superiority.

The experimental medication empagliflozin is administered as a 10 mg film-coated tablet via the oral route. This substance is utilized in the trial as part of the combination therapy or as a monotherapy.

The experimental medication BI 690517, also referred to as vicadrostat, is provided in a film-coated tablet pharmaceutical form for oral administration. This agent is evaluated in combination with empagliflozin.

A placebo matching vicadrostat is utilized as a comparator treatment in the study design to facilitate a double-blind assessment. This placebo is administered to participants receiving empagliflozin monotherapy to serve as a control against the combination therapy.

The primary efficacy assessment is the time to the first event of cardiovascular death or heart failure event, which is defined as hospitalization for heart failure or an urgent heart failure visit. Secondary efficacy parameters include the time to the first event of cardiovascular death or hospitalization for heart failure, as well as the time to the first occurrence of a composite outcome consisting of kidney disease progression, hospitalization for heart failure, and cardiovascular death.

Additional secondary endpoints involve:

• Time to the first event of the 4-point MACE, comprising cardiovascular death, heart failure event, non-fatal myocardial infarction, or non-fatal stroke.
• The time to the first event of new-onset atrial fibrillation or atrial flutter, or cardiovascular death, in participants without a history of these conditions.
• Time to all-cause death, cardiovascular death, or the first occurrence of hospitalization for heart failure.
• The time to the first event of new-onset heart failure or cardiovascular death.
• The occurrences of both first and recurrent hospitalizations for heart failure.
• The absolute change from baseline in mean systolic blood pressure or mean diastolic blood pressure at Week 24.
• The relative change from baseline in the urinary albumin-to-creatinine ratio at Week 24.
• The occurrences of all-cause hospitalizations.