Vericiguat Drug-drug Interaction With Nitroglycerin in Stable Coronary Artery Disease Patients

Study Overview
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Brief Summary
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This study is intended to investigate the effect of nitroglycerin on vericiguat in patients with stable coronary artery disease (CAD). Nitroglycerin is the standard therapy to treat acute crisis of angina. Thus there is a high likelihood of co-administration of both drugs in the target indication of vericiguat, worsening heart failure (HF). Therefore, it is important to investigate the safety and tolerability of vericiguat and nitroglycerin, which may be used as unprescribed on-demand treatment by patients with acute episodes of angina pectoris.

Official Title
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Evaluation of the Effect of 0.4 mg Nitroglycerin Spray After Pretreatment With Multiple Once Daily Oral Doses of 2.5 mg, 5 mg and 10 mg Vericiguat (BAY 1021189) Each Given Over 14 ± 3 Days on Safety, Tolerability and Blood Pressure in a Multi-center, Randomized, Placebo-controlled, Double-blind Group Comparison Study in Stable Coronary Artery Disease (CAD) Patients Aged 30 to 80 Years

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Vericiguat (BAY1021189)
* Drug: Placebo
* Drug: Nitroglycerin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with stable CAD defined by coronary artery stenosis in any of the 3 main coronary vessels > 50% documented by coronary angiography within last 36 months or history of myocardial infarction Age: 30 to 80 years Body mass index (BMI): above/equal 18.0 and below/equal 36.0 kg / m² Female subjects must be of non-childbearing potential Exclusion Criteria: Intervention e.g. revascularization by percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) during the last 3 months Progressive angina with symptoms of worsening of angina within the < 3 months History of recent (< 6 months prior to the first screening examination) myocardial infarction or unstable angina Symptomatic carotid stenosis, or transient ischemic attack or stroke within 3 months prior or patients with stroke at more than 3 months prior with significant residual neurologic involvement Insulin dependent diabetes mellitus Clinically relevant cardiac ischemia Clinical significant persistent ischemia Atrial fibrillation, pacemaker, defibrillator, atrial ventricular (AV)-block II and III Systolic blood pressure below 110 or above 160 mmHg Diastolic blood pressure above 100 mmHg Heart rate below 50 or above 100 beats / min Estimated glomerular filtration rate < 30 mL/min/1.73m2

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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: Vericiguat + Nitroglycerin<br>Co-administration of vericiguat and nitroglycerin | Drug: Vericiguat (BAY1021189)<br>* Vericiguat up-titration from 2.5 mg to 10 mg in an interval of 14 +/- 3 days: 2.5 mg vericiguat for 14 +/-3 days given as 2 x 1.25 mg tablets followed by 5 mg vericiguat for 14 +/-3 days given as 1 x 5 mg tablet followed by 10 mg vericiguat for 14 +/-3 days given as 2 x 5 mg tablets<br>Drug: Nitroglycerin<br>* 0.4 mg nitroglycerin spray administered at 2.5 hours before treatment (vericiguat [trough] or placebo) on day 12, day 26 and day 40 at 4 hours after treatment (vericiguat [peak] or placebo) on day 13, day 27 and day 41<br>|
| Placebo Comparator: Placebo + Nitroglycerin<br>Aministration of matching placebo and nitroglycerin. | Drug: Placebo<br>* Placebo for 14 +/-3 days given as 1 or 2 tablets [o.d.].<br>Drug: Nitroglycerin<br>* 0.4 mg nitroglycerin spray administered at 2.5 hours before treatment (vericiguat [trough] or placebo) on day 12, day 26 and day 40 at 4 hours after treatment (vericiguat [peak] or placebo) on day 13, day 27 and day 41<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as measure of safety and tolerability |  | approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Regular measurement of blood pressure (mmHg) in supine, sitting and standing position. | approximately 1 year | 
| Heart rate | Regular measurement of heart rate (bpm) in supine, sitting and standing position. | approximately 1 year |