A Double-blind Study to Investigate Efficacy, Safety and Tolerability of BAY1142524 in Patients With Type II Diabetes and a Clinical Diagnosis of Diabetic Kidney Disease

Study Overview
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Brief Summary
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The purpose of the trial is the analysis of safety and efficacy of the chymase inhibitor BAY1142524 at a dose of 25 mg BID in comparison to placebo using a 6 months treatment period in type II diabetic patients with a clinical diagnosis of diabetic kidney disease. BAY1142524 or placebo will be given on top of evidence-based standard of care for diabetic kidney disease. Primary objective is the analysis of first signs of efficacy as determined by favourable changes in urinary albumin creatinine ratio. Secondary objective is the analysis of safety and tolerability as evidenced by the incidence and severity of adverse events. 64 valid patients have to complete treatment with verum and 32 valid patients have to complete treatment with placebo.

Official Title
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A Randomized, Double-blind, Multicenter Study to Assess the Efficacy and Safety of a 6 Month Oral Treatment With the Chymase Inhibitor BAY 1142524 at a Dose of 25 mg BID in Comparison to Placebo on Top of Standard of Care in Patients With Type II Diabetes and a Clinical Diagnosis of Diabetic Kidney Disease

Conditions
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Diabetic Kidney Disease

Intervention / Treatment
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* Drug: Fulacimstat (BAY1142524)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Type 2 Diabetes Mellitus and a clinical diagnosis of diabetic kidney disease (DKD) (as judged by the investigator) who have finished their up-titration with an angiotensin receptor blocker (ARB) or an ACEI (angiotensin-converting enzyme inhibitor) to their maximum tolerated dose at least 3 months prior to the screening visit, whereby the maximum tolerated dose has to be at least as high as the minimal recommended dose of an ARB or ACEI according to local and/or international guidelines. Patients have to be treated with an ARB or ACEI, but not with both simultaneously, without any adjustments to this therapy for at least 4 weeks prior to the screening visit. UACR >50 mg/g and <3000 mg/g in 2 out of 3 consecutive morning void samples at the screening and the baseline visit estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m*2 and <90 mL/min/1.73 m*2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at the screening visit and the baseline visit Exclusion Criteria: Non-DKD if it is the main diagnosis contributory to chronic kidney disease (CKD), as judged by the investigator Known bilateral clinical relevant renal artery stenosis (>75%) New York Heart Association (NYHA) Class IV Acute kidney injury or dialysis within the last 3 months before the screening visit Renal replacement therapy during study conduct Renal allograft in place or a scheduled kidney transplant during study conduct Stroke, transient ischemic cerebral attack, acute coronary syndrome, or hospitalization for heart failure in the last 3 months prior to screening visit Clinically relevant hepatic dysfunction Uncontrolled hypertension as evidenced by systolic blood pressure >160 mmHg, diastolic blood pressure >100 mmHg (mean of triplicate values at the screening or baseline visit)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Fulacimstat (BAY1142524)<br>Patients have to have a clinical diagnosis of diabetic kidney disease and have to be treated with standard of care for this condition | Drug: Fulacimstat (BAY1142524)<br>* 25 mg BAY1142524 are given twice daily over a treatment period of 6 months<br>|
| Placebo Comparator: Placebo<br>Patients have to have a clinical diagnosis of diabetic kidney disease and have to be treated with standard of care for this condition | Drug: Placebo<br>* Matching placebo tablets are given twice daily over a treatment period of 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urinary albumin to creatinine ratio (UACR) | The ratio of albumin to creatinin will be determined in first morning void urine at baseline (before treatment start) and after 6 months of treatment | Baseline and at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment-emergent adverse event |  | From first intake of study drug up to 3 days after last administration of study drug | 
| Number of patients with serious adverse events |  | From first intake of study drug up to 3 days after last administration of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type II diabetes, diabetic kidney disease