Diabetic Kidney Disease
Conditions
Keywords
Type 2 Diabetes, Kidney diseases
Brief summary
The purpose of this study was to evaluate whether oral finerenone (study drug), in addition to standard daily therapy, is effective and safe in treating patients with type 2 diabetes mellitus and diabetic kidney disease, when compared to a placebo.
Interventions
10 mg or 20 mg Finerenone tablet to be given orally, once daily.
DRUGPlacebo
Matching placebo to be taken orally, once daily.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women ≥18 years of age * Subjects with Type Type 2 Diabetes Mellitus as defined by the American Diabetes Association * Diagnosis of Diabetic Kidney Disease with persistent high albuminuria or persistent very high albuminuria at the Run-In and Screening Visit * Pretreated with either angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at maximal tolerated labeled dose without adjustments * Serum potassium \<=4.8 mmol/L
Exclusion criteria
* Confirmed significant non-diabetic renal disease, including clinically relevant renal artery stenosis * Uncontrolled arterial hypertension (ie, mean sitting systolic blood pressure (SBP) ≥170 mmHg or mean sitting diastolic blood pressure(DBP) ≥110 mmHg at run in visit, or mean sitting SBP ≥160 mmHg or mean sitting DBP ≥100 mmHg at screening) * 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 \[class 1A recommendation for mineralcorticoid receptor antagonist (MRAs)\] * Dialysis for acute renal failure within 12 weeks of Run-in visit * Renal allograft in place or scheduled kidney transplant within next 12 months * Glycated hemoglobin (HbA1c) \>12%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non Fatal Stroke, or Hospitalization for Heart Failure. | From randomization up until the first occurrence of the CV composite endpoint, or censoring at the end of the study, with an average study duration of 41 months. | Number of participants with the first occurrence of the primary cardiovascular (CV) composite outcome, CV death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure were reported as descriptive result. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease of eGFR ≥40% From Baseline Over at Least 4 Weeks, or Renal Death. | From randomization up until the first occurrence of the renal composite endpoint, or censoring at the end of the study, with an average study duration of 41 months. | Number of participants with first occurrence of the composite endpoint of onset of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death were reported as descriptive result. |
| All-cause Hospitalization | From randomization up until the first occurrence of the hospitalization due to any cause, or censoring at the end of study, with an average study duration of 41 months | Number of participants with first occurrence of a hospitalization event were reported as descriptive result. |
| All-cause Mortality | From randomization up until death due to any cause, or censoring at the end of the study, with an average study duration of 41 months | Number of participants with death due to any cause were reported as descriptive result. Number of participants with outcome death reported here includes deaths occurred after randomization until the end of the study visit. Deaths after end of study visit are not included in this table. |
| Change in Urinary Albumin-to-creatine Ratio (UCAR) From Baseline to Month 4 | From baseline up until Month 4 | First morning void urine samples were collected to evaluate the urinary albumin-to-creatinine ratio (UACR). Month 4 was the visit closest to day 120 within a time window of 120 ± 30 days after randomization. If no measurements were available in this time window, the participant was excluded from this analysis. Ratio of UACR at Month 4 to UACR at baseline is reported as the change. |
| The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease in eGFR of ≥57% From Baseline Over at Least 4 Weeks, or Renal Death | From randomization up until the first occurrence of the renal composite endpoint, or censoring at the end of the study, with an average study duration of 41 months | Number of participants with first occurrence of the renal composite outcome, onset of kidney failure, a sustained decrease in eGFR of ≥57% from baseline over at least 4 weeks, or renal death were reported as descriptive result. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Puerto Rico, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Participant flow
Recruitment details
Study was conducted at multiple centers in 48 countries/regions between 17-Sep-2015 (first participant first visit) and 02-Feb-2021 (last participant last visit).
Pre-assignment details
Overall, 19381 participants were screened. Of them,11944 participants were screening failures and 7437 participants were randomized. 85 participants were prospectively excluded from the analyses due to critical GCP violations resulting in 7352 in full analysis set. 7341 participants received study treatment. 1 participant was assigned to placebo but received finerenone.
Participants by arm
| Arm | Count |
|---|---|
| Finerenone Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy | 3,686 |
| Placebo Participants received matching placebo once daily in addition to standard of care therapy | 3,666 |
| Total | 7,352 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | GCP violations | 37 | 48 |
| Overall Study | Lost to Follow-up | 4 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 7 |
Baseline characteristics
| Characteristic | Finerenone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.13 Years STANDARD_DEVIATION 9.67 | 64.13 Years STANDARD_DEVIATION 10 | 64.13 Years STANDARD_DEVIATION 9.83 |
| Estimated glomerular filtration rate (eGFR) | 67.62 mL/min/1.73m^2 STANDARD_DEVIATION 21.65 | 67.99 mL/min/1.73m^2 STANDARD_DEVIATION 21.74 | 67.80 mL/min/1.73m^2 STANDARD_DEVIATION 21.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 618 Participants | 603 Participants | 1221 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3058 Participants | 3057 Participants | 6115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 6 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 73 Participants | 70 Participants | 143 Participants |
| Race (NIH/OMB) Asian | 715 Participants | 739 Participants | 1454 Participants |
| Race (NIH/OMB) Black or African American | 113 Participants | 145 Participants | 258 Participants |
| Race (NIH/OMB) More than one race | 87 Participants | 86 Participants | 173 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 17 Participants | 14 Participants | 31 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 7 Participants | 16 Participants |
| Race (NIH/OMB) White | 2672 Participants | 2605 Participants | 5277 Participants |
| Sex: Female, Male Female | 1158 Participants | 1089 Participants | 2247 Participants |
| Sex: Female, Male Male | 2528 Participants | 2577 Participants | 5105 Participants |
| Urinary albumin-to-creatinine ratio (UACR) | 302.36 milligram/gram (mg/g) | 315.06 milligram/gram (mg/g) | 308.18 milligram/gram (mg/g) |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 339 / 3,686 | 383 / 3,666 |
| other Total, other adverse events | 1,797 / 3,683 | 1,717 / 3,658 |
| serious Total, serious adverse events | 1,158 / 3,683 | 1,215 / 3,658 |
Outcome results
Primary
The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non Fatal Stroke, or Hospitalization for Heart Failure.
Number of participants with the first occurrence of the primary cardiovascular (CV) composite outcome, CV death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure were reported as descriptive result.
Time frame: From randomization up until the first occurrence of the CV composite endpoint, or censoring at the end of the study, with an average study duration of 41 months.
Population: Full analysis set (FAS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Finerenone | The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non Fatal Stroke, or Hospitalization for Heart Failure. | 458 Participants |
| Placebo | The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non Fatal Stroke, or Hospitalization for Heart Failure. | 519 Participants |
p-value: 0.026495% CI: [0.76, 0.98]Log Rank
Secondary
All-cause Hospitalization
Number of participants with first occurrence of a hospitalization event were reported as descriptive result.
Time frame: From randomization up until the first occurrence of the hospitalization due to any cause, or censoring at the end of study, with an average study duration of 41 months
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Finerenone | All-cause Hospitalization | 1573 Participants |
| Placebo | All-cause Hospitalization | 1605 Participants |
p-value: 0.355895% CI: [0.9, 1.04]Log Rank
Secondary
All-cause Mortality
Number of participants with death due to any cause were reported as descriptive result. Number of participants with outcome death reported here includes deaths occurred after randomization until the end of the study visit. Deaths after end of study visit are not included in this table.
Time frame: From randomization up until death due to any cause, or censoring at the end of the study, with an average study duration of 41 months
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Finerenone | All-cause Mortality | 333 Participants |
| Placebo | All-cause Mortality | 370 Participants |
p-value: 0.133795% CI: [0.77, 1.04]Log Rank
Secondary
Change in Urinary Albumin-to-creatine Ratio (UCAR) From Baseline to Month 4
First morning void urine samples were collected to evaluate the urinary albumin-to-creatinine ratio (UACR). Month 4 was the visit closest to day 120 within a time window of 120 ± 30 days after randomization. If no measurements were available in this time window, the participant was excluded from this analysis. Ratio of UACR at Month 4 to UACR at baseline is reported as the change.
Time frame: From baseline up until Month 4
Population: Subjects in full analysis set with measurements available within the time window of Month 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Finerenone | Change in Urinary Albumin-to-creatine Ratio (UCAR) From Baseline to Month 4 | 0.624 Ratio |
| Placebo | Change in Urinary Albumin-to-creatine Ratio (UCAR) From Baseline to Month 4 | 0.922 Ratio |
p-value: <0.000195% CI: [0.65, 0.704]ANCOVA
Secondary
The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease in eGFR of ≥57% From Baseline Over at Least 4 Weeks, or Renal Death
Number of participants with first occurrence of the renal composite outcome, onset of kidney failure, a sustained decrease in eGFR of ≥57% from baseline over at least 4 weeks, or renal death were reported as descriptive result.
Time frame: From randomization up until the first occurrence of the renal composite endpoint, or censoring at the end of the study, with an average study duration of 41 months
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Finerenone | The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease in eGFR of ≥57% From Baseline Over at Least 4 Weeks, or Renal Death | 108 Participants |
| Placebo | The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease in eGFR of ≥57% From Baseline Over at Least 4 Weeks, or Renal Death | 139 Participants |
p-value: 0.040695% CI: [0.6, 0.99]Log Rank
Secondary
The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease of eGFR ≥40% From Baseline Over at Least 4 Weeks, or Renal Death.
Number of participants with first occurrence of the composite endpoint of onset of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death were reported as descriptive result.
Time frame: From randomization up until the first occurrence of the renal composite endpoint, or censoring at the end of the study, with an average study duration of 41 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Finerenone | The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease of eGFR ≥40% From Baseline Over at Least 4 Weeks, or Renal Death. | 350 Participants |
| Placebo | The First Occurrence of the Composite Endpoint of Onset of Kidney Failure, a Sustained Decrease of eGFR ≥40% From Baseline Over at Least 4 Weeks, or Renal Death. | 395 Participants |
p-value: 0.068995% CI: [0.76, 1.01]Log Rank