Coronary Artery Disease
Conditions
Brief summary
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.
Interventions
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
DRUGPlacebo
Placebo for 14 +/-3 days given as 1 or 2 tablets \[o.d.\].
DRUGNitroglycerin
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
Sponsors
Merck Sharp & Dohme LLC
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with adverse events as measure of safety and tolerability | approximately 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | approximately 1 year | Regular measurement of blood pressure (mmHg) in supine, sitting and standing position. |
| Heart rate | approximately 1 year | Regular measurement of heart rate (bpm) in supine, sitting and standing position. |
Countries
Germany
Outcome results
None listed