Safety and Efficacy of Different Oral Doses of BAY94-8862 in Japanese Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Nephropathy (ARTS-DN Japan)

Study Overview
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Brief Summary
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This study will be conducted in Japanese subjects with type 2 diabetes mellitus and the clinical diagnosis of Diabetic Nephropathy( DN) using a multi-center, randomized, adaptive, double-blind, placebo-controlled, parallel-group design. Primary objective of the study is investigate the change of Urinary Albumin to Creatine Ratio (UACR) after treatment with different oral doses of BAY94-8862 given once daily from baseline to Visit 8 (Day 90)

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 Japanese 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: BAY94-8862
* Drug: BAY94-8862
* Drug: BAY94-8862
* Drug: BAY94-8862
* Drug: BAY94-8862
* Drug: Placebo
* Drug: BAY 94-8862
* Drug: BAY 94-8862


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese subjects with type 2 diabetes mellitus and a clinical diagnosis of DN (Diabetic Nephropathy) treated with at least the minimal recommended dose of an Angiotensin Converting Enzyme Inhibitor (ACEI) and/or Angiotensin Receptor Blocker (ARB) 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/1.73 m2 Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) or Persistent high albuminuria defined as UACR of >/=30 mg/g but <300 mg/g (>/=3.4 mg/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/1.73 m2 (CKD-EPI) Serum potassium </=4.8 mmol/L at both the run-in visit and the screening visit Exclusion Criteria: Non-diabetic renal disease (confirmed by biopsy) Known bilateral clinically relevant renal artery stenosis (>75%) Glycated hemoglobin(HbA1c) >12% at the run-in visit or the screening visit UACR >3000 mg/g (339 mg/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 sitting 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

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY94-8862 (1.25 mg)<br> | Drug: BAY94-8862<br>* 1.25 mg BAY94-8862 tablet once daily in the morning<br>|
| Experimental: BAY94-8862 (2.5 mg)<br> | Drug: BAY94-8862<br>* 2.5 mg BAY94-8862 tablet once daily in the morning<br>|
| Experimental: BAY94-8862 (5 mg )<br> | Drug: BAY94-8862<br>* 5 mg BAY94-8862 tablet once daily in the morning<br>|
| Experimental: BAY94-8862 (7.5 mg)<br> | Drug: BAY94-8862<br>* 7.5 mg BAY94-8862 tablet once daily in the morning<br>|
| Experimental: BAY94-8862 (10 mg)<br> | Drug: BAY94-8862<br>* 10 mg BAY94-8862 tablet once daily in the morning<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo tablet once daily in the morning<br>|
| Experimental: BAY 94-8862 (15 mg)<br> | Drug: BAY 94-8862<br>* 15 mg BAY 94-8862 tablet once daily in the morning<br>|
| Experimental: BAY 94-8862 (20 mg)<br> | Drug: BAY 94-8862<br>* 20 mg BAY 94-8862 tablet once daily in the morning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of urinary albumin-to creatinine ratio |  | Baseline and 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum potassium concentration |  | Baseline and 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BAY94-8862, MR antagonist, Diabetic nephropathy, Japanese patients