Clinical Trials List
Protocol NumberBAY 94-8862 (finerenone) / 16244
NCT Number(ClinicalTrials.gov Identfier)NCT02540993
2015-11-16 - 2022-01-31
Phase III
Terminated9
ICD-10E11.22
Type 2 diabetes mellitus with diabetic chronic kidney disease
A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone on the reduction of cardiovascular morbidity and mortality in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease in addition to standard of care
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Trial Applicant
BAYER TAIWAN COMPANY LTD.
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Sponsor
Bayer
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- VIN-CENT Wu Division of Nephrology
- 吳明修 Division of Nephrology
- Kwan-Dun Wu Division of Nephrology
- 楊紹佑 Division of Nephrology
- 高芷華 Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 邱鼎育 Division of Nephrology
- 黃惠勇 Division of Nephrology
- 李岳庭 Division of Nephrology
- Chien-Hsing Wu Division of Nephrology
- 李隆志 Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Harn-Shen Chen Division of Nephrology
- 楊智宇 Division of Nephrology
The Actual Total Number of Participants Enrolled
13 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 蔡尚峰 Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- HSIANG-HAO HSU Division of Nephrology
- Guan-Hsing Chen Division of Nephrology
- 張明揚 Division of Nephrology
- 楊皇煜 Division of Nephrology
The Actual Total Number of Participants Enrolled
8 Stop recruiting
Audit
None
Co-Principal Investigator
- Hsi-Hsien Chen Division of Nephrology
- Chih-Chin Kao Division of Nephrology
- 林志弘 Division of Endocrinology
The Actual Total Number of Participants Enrolled
14 Stop recruiting
Audit
None
Condition/Disease
Diabetic kidney disease
Objectives
The primary objective of this study is to:
Demonstrate whether, in addition to standard of care (SoC),
finerenone is superior to placebo in delaying the time to first occurrence
of cardiovascular (CV) mortality and morbidity in subjects with type 2
diabetes mellitus (T2DM) and the clinical diagnosis of diabetic kidney
disease (DKD).
The secondary objectives of this study are to determine whether, in addition
to SoC, finerenone compared to placebo:
Delays the time to first occurrence of the following composite endpoint:
onset of kidney failure, a sustained decrease in estimated glomerular
filtration rate (eGFR) of ≥40% from baseline over at least 4 weeks or
renal death
Delays the time to all-cause hospitalization
Delays the time to all-cause mortality
Change in UACR from baseline to Month 4
Delays the time to first occurrence of the following composite endpoint:
onset of kidney failure, a sustained decrease in eGFR of ≥57% from
baseline over at least 4 weeks or renal death.
Test Drug
BAY 94-8862/ Finerenone
Active Ingredient
(4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide
Dosage Form
Tablet
Dosage
10mg, 20mg
Endpoints
Primary Outcome Measures :
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 [ Time Frame: From randomization up until the first occurrence of the primary renal composite endpoint, or censoring at the end of the study, with an average follow-up time of 32 months ]
Count of participants and time from randomization to the first occurrence of the primary renal composite outcome, onset of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.
Secondary Outcome Measures :
The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, or Hospitalization for Heart Failure [ Time Frame: From randomization up until the first occurrence of the key secondary CV composite endpoint, or censoring at the end of the study, with an average of 32 months ]
Count of participants and time from randomization to the first occurrence of the key secondary cardiovascular (CV) composite outcome, CV death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.
All-cause Mortality [ Time Frame: From randomization up until death due to any cause, or censoring at the end of the study visit, with an average of 32 months ]
Count of participants and time from randomization until death due to any cause were evaluated. Number of participants with outcome death is reported as descriptive result and hazard ratio is reported as statistical analysis. 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.
All-cause Hospitalization [ 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 of 32 months ]
Count of participants and time from randomization to the first occurrence of a hospitalization event were evaluated. Number of participants with the event is reported as descriptive result and hazard ratio is reported as statistical analysis.
Change in Urinary Albumin-to-creatinine Ratio (UACR) From Baseline to Month 4 [ Time Frame: 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 [ Time Frame: From randomization up until the first occurrence of the composite primary endpoint, or censoring at the end of the study, with an average of 32 months ]
Count of participants and time from randomization to the first occurrence of the secondary 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 evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.
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 [ Time Frame: From randomization up until the first occurrence of the primary renal composite endpoint, or censoring at the end of the study, with an average follow-up time of 32 months ]
Count of participants and time from randomization to the first occurrence of the primary renal composite outcome, onset of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.
Secondary Outcome Measures :
The First Occurrence of the Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, or Hospitalization for Heart Failure [ Time Frame: From randomization up until the first occurrence of the key secondary CV composite endpoint, or censoring at the end of the study, with an average of 32 months ]
Count of participants and time from randomization to the first occurrence of the key secondary cardiovascular (CV) composite outcome, CV death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure were evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.
All-cause Mortality [ Time Frame: From randomization up until death due to any cause, or censoring at the end of the study visit, with an average of 32 months ]
Count of participants and time from randomization until death due to any cause were evaluated. Number of participants with outcome death is reported as descriptive result and hazard ratio is reported as statistical analysis. 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.
All-cause Hospitalization [ 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 of 32 months ]
Count of participants and time from randomization to the first occurrence of a hospitalization event were evaluated. Number of participants with the event is reported as descriptive result and hazard ratio is reported as statistical analysis.
Change in Urinary Albumin-to-creatinine Ratio (UACR) From Baseline to Month 4 [ Time Frame: 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 [ Time Frame: From randomization up until the first occurrence of the composite primary endpoint, or censoring at the end of the study, with an average of 32 months ]
Count of participants and time from randomization to the first occurrence of the secondary 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 evaluated. Number of participants with the outcome event is reported as descriptive result and hazard ratio is reported as statistical analysis.
Inclution Criteria
Subjects must meet all of the following inclusion criteria to be included in the study:
1. Written informed consent signed before any study-specific procedure
2. Men or women aged 18 years and older. The lower age limit may be higher if legally required in the participating country.
3. Women of childbearing potential can only be included in the study if a pregnancy test is negative at the screening visit and if they agree to use adequate contraception. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: FSH levels > 40 mIU/mL and estradiol < 20 pg/mL] or have had surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy.
4. Subjects with type 2 diabetes mellitus as defined by the American Diabetes Association
5. Subjects with a clinical diagnosis of DKD based on either of the following criteria at the Run-in and Screening Visit:
•Persistent high albuminuria defined as UACR of >= 30 mg/g (>=3.4 mg/mmol) but < 300 mg/g (< 33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR >= 25 but <= 90 mL/min/1.73 m2 (CKD-EPI)
OR
•Persistent very high albuminuria defined as UACR of >=300 mg/g (>=33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR >=60 mL/min/1.73 m2 (CKD-EPI)
Note:One re-assessment of eGFR and UACR is allowed at the Run-in Visit and the Screening Visit. If one of the 3 UACR measurements is missing but the other 2 are valid, these values can be used to assess subject’s eligibility for this study.
6. Prior treatment with ACEIs and 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.
7. Serum potassium <= 4.8 mmol/L at both the Run-in and the Screening Visit
Note: One re-assessment of potassium is allowed at the Run-in and the Screening Visit.
8. Ability to understand and follow study-related instructions.
1. Written informed consent signed before any study-specific procedure
2. Men or women aged 18 years and older. The lower age limit may be higher if legally required in the participating country.
3. Women of childbearing potential can only be included in the study if a pregnancy test is negative at the screening visit and if they agree to use adequate contraception. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: FSH levels > 40 mIU/mL and estradiol < 20 pg/mL] or have had surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy.
4. Subjects with type 2 diabetes mellitus as defined by the American Diabetes Association
5. Subjects with a clinical diagnosis of DKD based on either of the following criteria at the Run-in and Screening Visit:
•Persistent high albuminuria defined as UACR of >= 30 mg/g (>=3.4 mg/mmol) but < 300 mg/g (< 33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR >= 25 but <= 90 mL/min/1.73 m2 (CKD-EPI)
OR
•Persistent very high albuminuria defined as UACR of >=300 mg/g (>=33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR >=60 mL/min/1.73 m2 (CKD-EPI)
Note:One re-assessment of eGFR and UACR is allowed at the Run-in Visit and the Screening Visit. If one of the 3 UACR measurements is missing but the other 2 are valid, these values can be used to assess subject’s eligibility for this study.
6. Prior treatment with ACEIs and 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.
7. Serum potassium <= 4.8 mmol/L at both the Run-in and the Screening Visit
Note: One re-assessment of potassium is allowed at the Run-in and the Screening Visit.
8. Ability to understand and follow study-related instructions.
Exclusion Criteria
Medical and surgical history
1. Known significant non-diabetic renal disease, including clinically relevant renal artery stenosis
2. UACR > 5000 mg/g (> 565 mg/mmol) at the Run-in Visit or Screening Visit
Note: One re-assessment is allowed in case UACR is > 5000 mg/g in one of the three urine samples collected at the Run-in Visit and the Screening Visit.
3. HbA1c > 12% (> 108 mmol/mol) at the Run-in Visit or Screening Visit
4. Uncontrolled arterial hypertension with mean sitting systolic blood pressure (SBP) >=170 mmHg or mean sitting diastolic blood pressure (DBP) 110 mmHg at the Run in Visit or mean sitting SBP >=160 mmHg or mean sitting DBP >=100 mmHg at the Screening Visit
5. Mean SBP < 90 mmHg at the Run-in Visit or at the Screening Visit
6. Subjects with a clinical diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association class II IV) at the Run in Visit (class 1A recommendation for MRAs)
7. Stroke, transient ischemic cerebral attack, acute coronary syndrome, or hospitalization for worsening heart failure, in the last 30 days prior to the Screening Visit
8. Dialysis for acute renal failure within 12 weeks prior to the Run-in Visit
9. Renal allograft in place or a scheduled kidney transplant within the next 12 months from the Run in Visit
10. Known hypersensitivity to the study treatment (active substance or excipients)
11. Addison’s disease
12. Hepatic insufficiency classified as Child-Pugh C
Medication and drug use
13. Concomitant therapy with eplerenone, spironolactone, any renin inhibitor, or potassium sparing diuretic which cannot be discontinued at least 4 weeks prior to the Screening Visit
14. Concomitant therapy with both ACEI and ARBs which cannot be discontinued for the purpose of the study
15. Concomitant therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or inducers (to be stopped at least 7 days before randomization)
Other
16. Any other condition or therapy, which would make the subject unsuitable for this study and will not allow participation for the full planned study period (e.g. active malignancy or other condition limiting life expectancy to less than 12 months)
17. Pregnant or breast-feeding or intention to become pregnant during the study
18. Previous assignment to treatment during this study or Study 16244
19. Previous (within 30 days prior to randomization) or concomitant participation in another clinical study (i.e. Phase I-III clinical studies) with investigational medicinal product(s), except for participation in the Run-in and Screening period of Study 16244
20. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site).
1. Known significant non-diabetic renal disease, including clinically relevant renal artery stenosis
2. UACR > 5000 mg/g (> 565 mg/mmol) at the Run-in Visit or Screening Visit
Note: One re-assessment is allowed in case UACR is > 5000 mg/g in one of the three urine samples collected at the Run-in Visit and the Screening Visit.
3. HbA1c > 12% (> 108 mmol/mol) at the Run-in Visit or Screening Visit
4. Uncontrolled arterial hypertension with mean sitting systolic blood pressure (SBP) >=170 mmHg or mean sitting diastolic blood pressure (DBP) 110 mmHg at the Run in Visit or mean sitting SBP >=160 mmHg or mean sitting DBP >=100 mmHg at the Screening Visit
5. Mean SBP < 90 mmHg at the Run-in Visit or at the Screening Visit
6. Subjects with a clinical diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association class II IV) at the Run in Visit (class 1A recommendation for MRAs)
7. Stroke, transient ischemic cerebral attack, acute coronary syndrome, or hospitalization for worsening heart failure, in the last 30 days prior to the Screening Visit
8. Dialysis for acute renal failure within 12 weeks prior to the Run-in Visit
9. Renal allograft in place or a scheduled kidney transplant within the next 12 months from the Run in Visit
10. Known hypersensitivity to the study treatment (active substance or excipients)
11. Addison’s disease
12. Hepatic insufficiency classified as Child-Pugh C
Medication and drug use
13. Concomitant therapy with eplerenone, spironolactone, any renin inhibitor, or potassium sparing diuretic which cannot be discontinued at least 4 weeks prior to the Screening Visit
14. Concomitant therapy with both ACEI and ARBs which cannot be discontinued for the purpose of the study
15. Concomitant therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or inducers (to be stopped at least 7 days before randomization)
Other
16. Any other condition or therapy, which would make the subject unsuitable for this study and will not allow participation for the full planned study period (e.g. active malignancy or other condition limiting life expectancy to less than 12 months)
17. Pregnant or breast-feeding or intention to become pregnant during the study
18. Previous assignment to treatment during this study or Study 16244
19. Previous (within 30 days prior to randomization) or concomitant participation in another clinical study (i.e. Phase I-III clinical studies) with investigational medicinal product(s), except for participation in the Run-in and Screening period of Study 16244
20. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site).
The Estimated Number of Participants
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Taiwan
101 participants
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Global
7437 participants
