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

NCT05254002
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Phase
Phase 2
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Recruitment status
Completed
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Participants
1,664
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Lead sponsor
Bayer
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Start date
2022-06-23
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Number of sites
173
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Summary
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.
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Acronym
CONFIDENCE
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Short title
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
clinicaltrials.gov
Official title
A Parallel-group Treatment, Phase 2, Double-blind, Three-arm Study to Assess Efficacy and Safety of Finerenone Plus Empagliflozin Compared With Either Finerenone or Empagliflozin Alone in Participants With Chronic Kidney Disease and Type 2 Diabetes.
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 2
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Study type
Interventional
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Completion date
2025-03-17
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First posted
2022-02-24
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Registry last updated
2026-07-13
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Primary completion date
2025-03-14
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Start date
2022-06-23
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Actual participants
1,664
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Participants
1,664
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
173
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Bayer
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05254002
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ClinicalTrials.gov ID
NCT05254002
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. 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

    Timeframe: Baseline and Day 180

    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.

  2. 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

    Timeframe: 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 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.

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

    Timeframe: Up to 210 days

    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.

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

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

    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.

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

    Timeframe: At Day 180

    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.

  4. Change From Baseline in eGFR at 30 Days

    Timeframe: At Day 30

    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.

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

    Timeframe: Up to 30 days

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

    Timeframe: At Day 180 and Day 210

    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.

  7. Number of Participants With AKI Events

    Timeframe: Up to 180 days

    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

  8. Total Number of AKI Events

    Timeframe: Up to 180 days

    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

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

    Timeframe: Up to 180 days

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

  10. Change From Baseline in K+

    Timeframe: At baseline, day 14 and day 180

    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.

  11. Number of Participants With Symptomatic Hypotension Events

    Timeframe: Up to 180 days

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

  12. Total Number of Symptomatic Hypotension Events

    Timeframe: Up to 180 days

    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.

  13. Number of Participants With Genital Mycotic Events

    Timeframe: Up to 180 days

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

  14. Total Number of Genital Mycotic Events

    Timeframe: Up to 180 days

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

  15. Number of Participants With Urosepsis and Pyelonephritis Events

    Timeframe: Up to 180 days

  16. Total Number of Urosepsis and Pyelonephritis Events

    Timeframe: Up to 180 days

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

  17. Number of Participants With Ketoacidosis Events

    Timeframe: Up to 180 days

  18. Total Number of Ketoacidosis Events

    Timeframe: Up to 180 days

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

  19. Number of Participants With Necrotizing Fasciitis of the Perineum Events

    Timeframe: Up to 180 days

  20. Number of Participants With Severe Hypoglycemia Events

    Timeframe: Up to 180 days

    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.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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.

  • 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).
Sources for eligibility
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  • Southwest Kidney Institute, PLC - SupriseSurprise, United States
  • Academic Medical Research InstituteLos Angeles, United States
  • Dignity Health Northridge Hospital Medical Center - NephrologyNorthridge, United States
  • Olive View - UCLA Medical CenterSylmar, United States
  • Touro University California - Metabolic Research CenterVallejo, United States
  • Florida Kidney Physicians - Delray Beach NephrologyDelray Beach, United States
  • West Orange Endocrinology & Clinical ResearchOcoee, United States
  • Innovative Research InstitutePort Charlotte, United States
  • Metabolic Research Institute, Inc.West Palm Beach, United States
  • Grady Memorial Hospital - EndocrinologyAtlanta, United States
  • Southeast Kidney Associates - East PointEast Point, United States
  • Velocity Clinical Research - SavannahSavannah, United States
  • Nola Care Clinical ResearchMetairie, United States
  • Omega Clinical Research - MetairieMetairie, United States
  • South Shore NephrologyPlymouth, United States
  • Lake Michigan NephrologySaint Joseph, United States
  • Oakland Medical ResearchTroy, United States
  • Clinical Research Consultants, a JCCT CompanyKansas City, United States
  • Kansas City VA Medical Center - EndocrinologyKansas City, United States
  • Center for Advanced Medicine - Diabetes CenterSt Louis, United States
  • St. Louis Heart and Vascular, PC - Christian Hospital OfficeSt Louis, United States
  • Somnos Clinical ResearchLincoln, United States
  • Healor Primary Care / CCT ResearchLas Vegas, United States
  • CCT Research - Santa Rosa Medical Centers of NevadaLas Vegas, United States
  • Circuit Clinical/Crystal RunMiddletown, United States

And 148 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-506981-30-00
  • 2021-003037-11
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (3)

Targets (2)