Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Finerenone (BAY94-8862); Placebo
Intervention description: Oral tablet; starting dose at 10 mg for subjects with an eGFR between 25 to < 60 mL/min/1.73m² at the Screening Visit; starting dose at 20 mg for subjects with an eGFR ≥ 60 mL/min/1.73m² at the Screening Visit; dose could be up-titrated from Month 1 onwards or down-titrated at any time during the study; once daily in the morning, until the trial was completed provided there were no safety grounds for discontinuing treatment; Matching placebo, oral tablet, once daily in the morning, until the trial was completed provided there were no safety grounds for discontinuing treatment
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 5734.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CKD; Diabetic Kidney Disease; Type 2 Diabetes; Kidney diseases

Summary:

      The primary objective of this study was to demonstrate whether, in addition to standard of
      care, finerenone is superior to placebo in delaying the progression of kidney disease, as
      measured by the composite endpoint of time to first occurrence of kidney failure, a sustained
      decrease of estimated glomerular filtration rate (eGFR) ≥40% from baseline over at least 4
      weeks, or renal death.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men or women ≥18 years of age

          -  Type 2 diabetes mellitus (T2D) as defined by the American Diabetes Association

          -  Diagnosis of chronic kidney disease (CKD) with at least one of the following criteria
             at run-in and screening visits:

               -  persistent high albuminuria (UACR ≥30 to <300 mg/g in 2 out of 3 first morning
                  void samples) and estimated glomerular filtration rate (eGFR) ≥25 but <60
                  mL/min/1.73 m² (CKD EPI) and presence of diabetic retinopathy or

               -  persistent very high albuminuria (UACR ≥300 mg/g in 2 out of 3 first morning void
                  samples) and eGFR ≥25 to <75 mL/min/1.73 m² (CKD-EPI)

          -  Prior treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin
             receptor blockers (ARBs) as follows:

               -  For at least 4 weeks prior to the run-in visit, subjects should be treated with
                  either an ACEI or ARB, or both

               -  Starting with the run-in visit, subjects should be treated with only an ACEI or
                  ARB

               -  For at least 4 weeks prior to the screening visit, subjects should be treated
                  with the maximum tolerated labeled dose (but not below the minimal labeled dose)
                  of only an ACEI or an ARB (not both) preferably without any adjustments to dose
                  or choice of agent or to any other antihypertensive or antiglycemic treatment

          -  Serum potassium ≤4.8 mmol/L at both the run-in and the screening visit

        Exclusion Criteria:

          -  Known significant non-diabetic renal disease, including clinically relevant renal
             artery stenosis

          -  Uncontrolled arterial hypertension (ie, mean sitting systolic blood pressure (SBP)
             ≥170 mmHg, sitting diastolic blood pressure (DBP) ≥110 mmHg at run-in visit, or mean
             sitting SBP ≥160 mmHg, sitting DBP ≥100 mmHg at screening)

          -  Glycated hemoglobin (HbA1c) >12%

          -  Mean SBP < 90 mmHg at the run-in visit or at the screening visit

          -  Clinical diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) and
             persistent symptoms (New York Heart Association [NYHA] class II - IV) at run-in visit
             (class 1A recommendation for mineralcorticoid receptor antagonists [MRAs])

          -  Stroke, transient ischemic cerebral attack, acute coronary syndrome, or
             hospitalization for worsening heart failure, in the last 30 days prior to the
             screening visit

          -  Dialysis for acute renal failure within 12 weeks of run-in visit

          -  Renal allograft in place or scheduled within next 12 months from the run-in visit