Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Nephropathy

Study Overview
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Brief Summary
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To assess a new drug, BAY94-8862 given orally at different doses, to evaluate whether it was safe and can help the well being of patients with type 2 diabetes and diabetic nephropathy. These treatment doses were compared to placebo.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Nephropathy

Conditions
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Diabetic Nephropathies

Intervention / Treatment
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* Drug: Finerenone (BAY94-8862)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18 years and older.The lower age limit may be higher if legally required in the participating country Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active. Subjects with type 2 diabetes mellitus fulfilling at least 1 of the following criteria are on oral antidiabetics and / or insulin, have a documented fasting glucose >/= 7.0 mmol/L in the medical history, have a 2 hour plasma glucose >/=11.1 mmol/L during an oral glucose tolerance test in the medical history, or have a glycated hemoglobin (HbA1c) >/=6.5% [National Glycohemoglobin Standardization Program (NGSP) / Diabetes Control and Complications Trial (DCCT)] in the medical history or at the run-in visit Subjects with a clinical diagnosis of diabetic nephropathy (DN) based on at least 1 of the following criteria: Persistent very high albuminuria defined as urinary albumin-to-creatine ratio (UACR) of >/=300 mg/g ( >/= 34 mg/mmol) in 2 out of 3 first morning void samples and estimated glomerular filtration rate (eGFR) >/=30 mL/min/1.73 m² but < 90 mL/min/1.73m² (Chronic Kidney Disease Epidemiology Collaboration, CKD EPI) (mL = milliliter; min = minute; m2 = square meter; g = gram; mmol = millimole) or Persistent high albuminuria defined as UACR of >/=30 mg/g but <300 mg/g in (>/=3.4mg/mmol but <34 mg/mmol) in 2 out of 3 first morning void samples and eGFR >/=30 mL/min/1.73 m² but < 90 mL/min/1.73m² Subjects treated with an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) for at least 3 months without any adjustments to this therapy for at least 4 weeks prior to the screening visit Serum potassium </= 4.8 mmol/L at both the run-in visit and the screening visit Exclusion Criteria: Non-diabetic renal disease Glycated hemoglobin (HbA1c) >12% at the run-in visit or the screening visit UACR >3000 mg/g (339mg/mmol) in any of the urinary first morning void samples at the run-in visit or screening visit Hypertension with mean sitting systolic blood pressure (SBP) >/=180 mmHg or mean sitting diastolic blood pressure (DBP) >/=110 mmHg at the run-in visit or mean supine SBP >/=160 mmHg or mean sitting DBP >/=100 mmHg at the screening visit Subjects with a clinical diagnosis of heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association class II-IV) at the run-in visit Concomitant therapy with eplerenone, spironolactone, any renin inhibitor, or potassium-sparing diuretic Dialysis for acute renal failure within the previous 6 months prior to the run-in visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Finerenone (BAY94-8862) (1.25 mg)<br>1.25 mg dose oral once daily for 90 days | Drug: Finerenone (BAY94-8862)<br> <br> |
| Experimental: Finerenone (BAY94-8862)(2.5 mg)<br>2.5 mg dose oral once daily for 90 days | Drug: Finerenone (BAY94-8862)<br> <br> |
| Experimental: Finerenone (BAY94-8862)(5 mg)<br>5 mg dose oral once daily for 90 days | Drug: Finerenone (BAY94-8862)<br> <br> |
| Experimental: Finerenone (BAY94-8862)(7.5 mg)<br>7.5 mg dose oral once daily for 90 days | Drug: Finerenone (BAY94-8862)<br> <br> |
| Experimental: Finerenone (BAY94-8862) (10 mg)<br>10 mg dose oral once daily for 90 days | Drug: Finerenone (BAY94-8862)<br> <br> |
| Experimental: Finerenone (BAY94-8862) (15 mg)<br>15 mg dose oral once daily for 90 days | Drug: Finerenone (BAY94-8862)<br> <br> |
| Experimental: Finerenone (BAY94-8862)(20 mg)<br>20 mg dose oral once daily for 90 days | Drug: Finerenone (BAY94-8862)<br> <br> |
| Placebo Comparator: Placebo<br>Placebo oral dose once daily for 90 days | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of UACR at Day 90 to UACR at Baseline | Albumin-to-creatinine ratio (UACR) is defined as gram of albumin per kilogram of creatinine. UACR was calculating the average of 3 first morning void samples taken on 3 consecutive days. | Baseline and Day 90±2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Day 90 in Serum Potassium |  | Baseline and Day 90±2 | 
| Change From Baseline to Day 90 in eGFR | An estimated glomerular filtration rate (eGFR) indicates the renal function. An eGFR was calculated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. | Baseline and Day 90±2 | 
| Change From Baseline to Day 90 in KDQOL-36 Domain Score (Effects of Kidney Disease) | The Kidney Disease QOL [KDQOL]-36 questionnaire is a specific measure of Health-Related Quality of Life (HRQoL) for chronic kidney disease (CKD) that includes effects and burden of kidney disease as well as physical and mental health scores. Index score ranges from 0 (severe problems in all items) to 100 (no problem in all items). Effects of Kidney disease subscore was analyzed. | Baseline and Day 90±2 | 
| Change From Baseline to Day 90 in EQ-5D Scores (EQ5D - Visual Analog Scale) | EuroQol Group 5-Dimension, 3-Level (EQ-5D-3L) questionnaires consist of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. EQ VAS was analyzed for this endpoint and it ranges from 0 (worst possible health state) to 100 (best possible health state). | Baseline and Day 90±2 |