A Double-blind Study to Investigate Efficacy, Safety and Tolerability of BAY 1142524 in Patients After Acute Myocardial Infarction With Left-ventricular Dysfunction

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 patients with left-ventricular (LV) dysfunction after myocardial infarction (MI). BAY1142524 or placebo will be given on top of evidence-based standard of care for left-ventricular dysfunction after myocardial infarction. Primary objective is the analysis of first signs of efficacy as determined by favourable changes in functional parameters of adverse cardiac remodelling (i.e. endsystolic and enddiastolic volume index, ejection fraction). Secondary objective is the analysis of safety and tolerability as evidenced by the incidence and severity of adverse events. 30 patients have to complete treatment with verum and 30 patients have to complete treatment with placebo.

Official Title
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A Randomized, Double-blind, Multicenter Study to Assess the Safety and Efficacy 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 Reduced Left-ventricular Ejection Fraction (LVEF≤ 45%) After Acute Myocardial Infarction

Conditions
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Myocardial Infarction

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 first ST elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI) or thrombolysis within 24 hours after symptom onset Diagnosis of STEMI requires the presence of the following three criteria: Typical clinical symptoms such as chest pain, shortness of breath for more than 20 minutes related to the myocardial infarction New ST elevation indicating myocardial infarction Significant elevation in troponin T or I with at least one value above the 99th percentile upper reference limit (URL) and/or elevation creatine kinase (CK) and creatine kinase MB (6-10% of total CK) At the screening period, on day 5 to 9 after MI, patients have to have a LVEF ≤ 45% and an infarct size >10% LV mass (as measured by LGE-MRI, central-blinded evaluation) Exclusion Criteria: Contraindication to perform contrast-enhanced cardiac MRI LVEF < 20% History of heart failure or LVEF < 50% before occurrence of the first STEMI Infarct size > 45% (g/g; LV mass) between 5 and 9 days after myocardial infarction NYHA (New York Heart Association) class IV at randomization Any planned cardiac intervention after baseline MRI or any other planned operations Non-ischemic causes for cardiomyopathy Diagnosis of atrial fibrillation Systolic blood pressure < 100 mm Hg or > 180 mm Hg; diastolic blood pressure < 50 mm Hg or >110 mm Hg, heart rate < 50 or >100 beat/minute; mean of triplicate values at randomization Clinically relevant hepatic dysfunction

Ages Eligible for Study
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Minimum Age: 40 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>30 patients with left-ventricular dysfunction after acute myocardial infarction | Drug: Fulacimstat (BAY1142524)<br>* 25 mg BAY 1142524 are given twice daily over a treatment period of 6 months<br>|
| Placebo Comparator: Placebo<br>30 patients with left-ventricular dysfunction after acute myocardial infarction | 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 left-ventricular ejection fraction (LVEF) |  | At 6 months | 
| Change in end diastolic volume index (EDVI) |  | At 6 months | 
| Change in end systolic volume index (ESVI) |  | At 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | Up to 7 months | 
| Number of patients with serious adverse events |  | Up to 7 months |