Vericiguat Drug-drug Interaction Study With Isosorbite Mononitrate in Stable Coronary Artery Disease Patients (VISOR)

Bayer

Status and phase: Completed; Phase 1

Conditions: Coronary Artery Disease

Treatments: Drug: Placebo; Drug: Vericiguat (BAY1021189); Drug: Isosorbide mononitrate (ISMN)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03255512

18582

2016-005178-36 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 41 patients

Sex: All

Ages: 30 to 80 years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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41 participants in 2 patient groups, including a placebo group

Vericiguat + isosorbite mononitrate

Experimental group

Description:

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).

Treatment:

Drug: Isosorbide mononitrate (ISMN)

Drug: Vericiguat (BAY1021189)

Placebo + isosorbite mononitrate

Placebo Comparator group

Description:

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).

Treatment:

Drug: Isosorbide mononitrate (ISMN)

Drug: Placebo