A Study to Learn How Well the Treatment Combination of Finerenone and Empagliflozin Works and How Safe it is Compared to Each Treatment Alone in Adult Participants With Long-term Kidney Disease (Chronic Kidney Disease) and Type 2 Diabetes

Bayer1,664 enrolled

Overview

Finerenone works by blocking a group of proteins, called mineralocorticoid receptor. An increased stimulation of mineralocorticoid receptor is known to trigger injury and inflammation in the kidney and is therefore thought to play a role in CKD. Empagliflozin lowers blood sugar levels by increasing the excretion of glucose from the blood into the urine. In this study, the researchers want to learn how well the combination of finerenone and empagliflozin helps to slow down the worsening of the participants' kidney function compared to either treatment alone. For this, the level of protein in the urine will be measured. The investigators also want to know how safe the combination is compared to either treatment alone. Depending on the treatment group, the participants will either take the combination of finerenone and empagliflozin, or finerenone together with a placebo, or empagliflozin together with a placebo, once a day as tablets by mouth. A placebo looks like a treatment but does not have any medicine in it. Importantly, the participants will also continue to take their other current medicine for CKD and T2D. The participants will be in the study for up to 7.5 months and will take the study treatments for 6 months. During the study, participants will visit the study site 7 times. The study team will: * collect blood and urine samples * check the participants' vital signs * do a physical examination including height and weight * check the participants' heart health by using an electrocardiogram (ECG) * monitor the participants' blood pressure * ask the participants questions about how they are feeling and what adverse events they may be having An adverse event is any problem that happens during the trial. Doctors keep track of all events that happen in trials, even if they do not think the events might be related to the study treatments.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Interventions

Finerenone (BAY94-8862 ) 10 mgDRUG

oral administration, once daily if screening eGFR (Estimated glomerular filtration rate) results are: \<60 mL/min/1.73 m2

EmpagliflozinDRUG

oral administration, once daily

Empagliflozin PlaceboDRUG

Matching placebo to empagliflozin oral administration, once daily

Finerenone (BAY94-8862 ) 20 mgDRUG

oral administration, once daily if screening eGFR (Estimated glomerular filtration rate) results are: ≥60 mL/min/1.73 m2

Finerenone PlaceboDRUG

Matching Placebo to Finerenone oral administration once daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participant with a clinical diagnosis of chronic kidney disease (CKD) and the following: * In Part A: eGFR 40-90 ml/min/1.73m\^2 (with no more than 20% having an eGFR \>75 ml/min/1.73m\^2) using Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula at screening visit and at least one historical value of eGFR \<60 mL/min/1.73 m\^2 within 3 months or have a registered diagnosis of CKD. * In Part B: eGFR 30-90 ml/min/1.73m\^2 (with no more than 20% having an eGFR \>75 ml/min/1.73m\^2) using CKD-EPI formula at screening visit and at least one historical value of eGFR \<60 mL/min/1.73 m\^2 within 3 months or have a registered diagnostic of CKD. * 100 ≤UACR \<5000 mg/g at screening visit (mean value from 3 morning void samples) and documentation of albuminuria/proteinuria (quantitative or semi-quantitative measurement) in the participant's medical records at least 3 months prior to screening * Participant with type 2 diabetes (T2D) as defined by the American Diabetes Association (ADA 2021), with glycated hemoglobin (HbA1c) at screening \<11%. * Participant treated with the clinically maximum tolerated dose, as per investigator judgment, of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), but not both, for more than 1 month at screening visit. Exclusion Criteria: * Participants with type 1 diabetes (T1D). * Participant with hepatic insufficiency classified as Child-Pugh C. * Participant with blood pressure at Day 1 visit (Visit 2) higher than 160 systolic blood pressure (SBP) or 100 diastolic blood pressure (DBP) or SBP lower than 90 mmHg. * Participant currently treated with a sodium/glucose cotransporter-2 inhibitor (SGLT2i) or SGLT-1/2i or who received a SGLT2i or SGLT-1/2i which cannot be discontinued at least 8 weeks prior to the screening visit and during study intervention treatment. * Participant treated with another mineralocorticoid receptor antagonist (MRA) (e.g., eplerenone, esaxerenone, spironolactone, canrenone), a renin inhibitor, potassium supplements, a potassium sparing diuretic (e.g., amiloride, triamterene), a potassium binder agent, or angiotensin receptor-neprilysin inhibitor (ARNI) which cannot be discontinued at least 8 weeks prior to the screening visit and during study intervention treatment. * Participants currently treated or who were treated with Finerenone (Kerendia©) within 8 weeks prior to the screening visit. * Participant with serum/plasma potassium (K+) above 4.8 mmol/L at screening visit (central laboratory value).

Locations (173)

Southwest Kidney Institute, PLC - Suprise

Surprise, Arizona, United States

Academic Medical Research Institute

Los Angeles, California, United States

Dignity Health Northridge Hospital Medical Center - Nephrology

Northridge, California, United States

Olive View - UCLA Medical Center

Sylmar, California, United States

Touro University California - Metabolic Research Center

Vallejo, California, United States

Outcomes

Primary Outcomes

Least Squares Mean Ratio of Urinary Albumin-to-Creatinine Ratio (UACR) at Day 180 Relative to Baseline in the Combination Therapy Group Versus Empagliflozin Alone

Least squares mean ratio of urinary albumin-to-creatinine ratio (UACR) at Day 180 relative to baseline, estimated using a mixed model for repeated measures. The treatment effect is expressed as the ratio of LS means for the combination therapy group compared with empagliflozin alone. A ratio below 1 indicates a reduction in UACR relative to baseline. UACR is a marker of albuminuria and a predictor of long-term renal and cardiovascular outcomes in participants with chronic kidney disease and type 2 diabetes.

Time frame: Baseline and Day 180

Least Squares Mean Ratio of Urinary Albumin-to-Creatinine Ratio (UACR) at Day 180 Relative to Baseline in the Combination Therapy Group Versus Finerenone Alone

Least squares mean ratio of urinary albumin-to-creatinine ratio (UACR) at Day 180 relative to baseline in the combination therapy group compared with finerenone alone, estimated using a mixed model for repeated measures. A ratio below 1 indicates a reduction in UACR relative to baseline. UACR is a measurement of albuminuria and a predictor of long-term renal and cardiovascular outcomes in participants with type 2 diabetes.

Time frame: Baseline and Day 180

Secondary Outcomes

Least Squares Mean Ratio of Urinary Albumin-to-Creatinine Ratio (UACR) at Day 210 Relative to Day 180

Least squares mean ratio of urinary albumin-to-creatinine ratio (UACR) at Day 210 (30 days after stopping the treatment) relative to Day 180, estimated using a mixed model for repeated measures. A ratio above 1 indicates an increase in UACR at Day 210 compared with Day 180. UACR is a measurement of albuminuria, a predictor of long-term renal and cardiovascular outcomes in participants with type 2 diabetes.

Time frame: Up to 210 days

Least Squares Mean Ratio of Urinary Albumin-to-Creatinine Ratio (UACR) at 30 Days After End of Treatment Relative to Baseline

Least squares mean ratio of urinary albumin-to-creatinine ratio (UACR) relative to baseline, estimated using a mixed model for repeated measures. A ratio below 1 indicates a reduction in UACR relative to baseline. UACR is a marker of albuminuria and a predictor of long-term renal and cardiovascular outcomes in participants with type 2 diabetes.

Time frame: Baseline to Day 210 (30 days after End of Treatment)

Number of Participants by Relative Change in UACR Category at Day 180 (>30%, >40%, >50%)

This outcome summarizes the number of participants whose relative change from baseline in urine albumin-to-creatinine ratio (UACR) at Day 180 met prespecified category thresholds (\>30%, \>40%, or \>50%). Relative change was assessed based on baseline and post-baseline UACR measurements. Percentages were calculated using as denominator the number of participants with both a baseline and at least one post-baseline UACR assessment within the specified timeframe. Participants were classified independently within each category.

Time frame: At Day 180

Change From Baseline in eGFR at 30 Days

Change from baseline to Day 30 in estimated glomerular filtration rate (eGFR) was evaluated for each treatment group. Change was calculated as the value at Day 30 minus the baseline value. Negative values indicate a decrease from baseline and positive values indicate an increase from baseline.

Time frame: At Day 30

Number of Participants With an eGFR Decline Greater Than 30% at 30 Days From Baseline

Time frame: Up to 30 days

Change in eGFR at 180 Days and 210 Days From Day 30

Change in estimated glomerular filtration rate (eGFR) from Day 30 to Day 180 and Day 210 was evaluated for each treatment group. Change was calculated as the value at Day 180 or Day 210 minus the value at Day 30. Positive values indicate an increase from Day 30 and negative values indicate a decrease from Day 30.

Time frame: At Day 180 and Day 210

Number of Participants With AKI Events

AKI is defined as any of the following: * An increase in serum creatinine by greater than or equal to 0.3 mg/dL within 48 hours; or * An increase in serum creatinine by greater than or equal to 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or * A urine volume less than 0.5 ml/kg/h for 6 hours Total number of AKI events Up to 180 days

Time frame: Up to 180 days

Total Number of AKI Events

Time frame: Up to 180 days

Number of Participants With Hyperkalemia Events (Moderate Hyperkalemia [5.5 <K+ ≤6.0 mmol/L], Severe Hyperkalemia [K+ >6.0 mmol/L])

Moderate hyperkalemia was defined as K+ \>5.5 to ≤6.0 mmol/L and severe hyperkalemia was defined as K+ \>6.0 mmol/L).

Time frame: Up to 180 days

Change From Baseline in K+

Serum potassium values (mmol/L) were assessed at baseline and scheduled post-baseline visits. Results are presented as observed mean potassium concentrations at each time point.

Time frame: At baseline, day 14 and day 180

Number of Participants With Symptomatic Hypotension Events

Number of participants who experienced at least one symptomatic hypotension event during the study period

Time frame: Up to 180 days

Total Number of Symptomatic Hypotension Events

Symptomatic hypotension events were assessed at all study visits and were documented as adverse events. The outcome represents the total number of symptomatic hypotension events reported during the study period.

Time frame: Up to 180 days

Number of Participants With Genital Mycotic Events

The outcome represents the number of participants who experienced at least one genital mycotic event during the study period.

Time frame: Up to 180 days

Total Number of Genital Mycotic Events

Occurrence of urinary tract infection events were assessed at all study visits and documented as AEs.

Time frame: Up to 180 days

Number of Participants With Urosepsis and Pyelonephritis Events

Time frame: Up to 180 days

Total Number of Urosepsis and Pyelonephritis Events

Occurrence of urosepsis and pyelonephritis events were assessed at all study visits and documented as AEs.

Time frame: Up to 180 days

Number of Participants With Ketoacidosis Events

Time frame: Up to 180 days

Total Number of Ketoacidosis Events

Occurrence of ketoacidosis events were assessed at all study visits and documented as AEs.

Time frame: Up to 180 days

Number of Participants With Necrotizing Fasciitis of the Perineum Events

Time frame: Up to 180 days

Number of Participants With Severe Hypoglycemia Events

Severe hypoglycemia was defined as glucose level of \<3.0 mmol/L (\<54 mg/dL) is sufficiently low to indicate serious, clinically important hypoglycemia. In addition, severe hypoglycemia, as defined by the ADA denotes severe cognitive impairment requiring external assistance for recovery.

Time frame: Up to 180 days

A Study to Learn How Well the Treatment Combination of Finerenone and Empagliflozin Works and How Safe it is Compared to Each Treatment Alone in Adult Participants With Long-term Kidney Disease (Chronic Kidney Disease) and Type 2 Diabetes

Overview

Conditions

Interventions

Eligibility

Locations (173)

Outcomes

Primary Outcomes

Secondary Outcomes