Vericiguat Drug-drug Interaction Study With Isosorbite Mononitrate in Stable Coronary Artery Disease Patients
Phase 1
Completed
- Conditions
- Coronary Artery Disease
- Interventions
- Registration Number
- NCT03255512
- Lead Sponsor
- Bayer
- Brief Summary
This study is intended to investigate the pharmacodynamic drug-drug interaction as well as the safety and tolerability of isosorbite mononitrate and vericiguat in patients with stable coronary artery disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
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 (inclusive) at the first screening examination
- Body mass index (BMI): above/equal 18.0 and below/equal 36.0 kg / m²
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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 prior to the first screening examination
- 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 to the first screening examination or patients with stroke at more than 3 months prior to the first screening examination with significant residual neurologic involvement
- Insulin dependent diabetes mellitus
- Clinically relevant cardiac ischemia at screening
- Clinical significant persistent ischemia, which should be ruled out by clinical judgment of the investigator, based on medical history, available clinical data e.g. past angiograms or preexisting or current exercise testing with any imaging technique (e.g. dobutamine stress echocardiography, adenosine or dobutamine stress cardiac magnetic resonance imaging (CMR), scinthigraphy or exercise ECG)
- Atrial fibrillation, pacemaker, defibrillator, atrial ventricular (AV)-block II and III
- Systolic blood pressure below 110 or above 160 mmHg at first screening visit
- Diastolic blood pressure above 100 mmHg at first screening visit
- Heart rate below 50 or above 100 beats / min (taken from ECG measurement) at first screening visit
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m*2 at first screening visit
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vericiguat + isosorbite mononitrate Isosorbide mononitrate (ISMN) Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each,prior to start of vericiguat administration. Then subjects received 2.5 mg vericiguat for about 14 days, followed by 5 mg vericiguat for about 14 days, followed by 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of vericiguat administration, taken 1 hour prior to vericiguat (in-house days) or together with vericiguat (out-patient days). Vericiguat + isosorbite mononitrate Vericiguat (BAY1021189) Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each,prior to start of vericiguat administration. Then subjects received 2.5 mg vericiguat for about 14 days, followed by 5 mg vericiguat for about 14 days, followed by 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of vericiguat administration, taken 1 hour prior to vericiguat (in-house days) or together with vericiguat (out-patient days). Placebo + isosorbite mononitrate Placebo Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each, prior to start of placebo administration. Then subjects received placebo matching 2.5 mg vericiguat for about 14 days, followed by placebo matching 5 mg vericiguat for about 14 days, followed by placebo matching 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of placebo administration, taken 1 hour prior to placebo (in-house days) or together with placebo (out-patient days). Placebo + isosorbite mononitrate Isosorbide mononitrate (ISMN) Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each, prior to start of placebo administration. Then subjects received placebo matching 2.5 mg vericiguat for about 14 days, followed by placebo matching 5 mg vericiguat for about 14 days, followed by placebo matching 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of placebo administration, taken 1 hour prior to placebo (in-house days) or together with placebo (out-patient days).
- Primary Outcome Measures
Name Time Method Blood pressure Up to 8 weeks Regular measurements of blood pressure after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.
Heart rate Up to 8 weeks Regular measurements heart rate after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events Up to 9 weeks
Trial Locations
- Locations (6)
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Medizinische Einrichtungen der Universität Bonn
🇩🇪Bonn, Nordrhein-Westfalen, Germany
SocraTec R&D GmbH
🇩🇪Erfurt, Thüringen, Germany
Charité - Campus Virchow-Klinikum (CVK)
🇩🇪Berlin, Germany
Universitätsklinikum Hamburg Eppendorf (UKE)
🇩🇪Hamburg, Germany
Universitätsherzzentrum Freiburg - Bad Krozingen
🇩🇪Bad Krozingen, Baden-Württemberg, Germany