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

Multi-center, Randomized, Placebo-controlled, Double-blind Group Comparison Study to Investigate Safety, Tolerability and Blood Pressure of 2.5 mg, 5.0 mg and 10 mg Vericiguat Each Given Over 14 ± 3 Days Together With Isosorbite Mononitrate (ISMN) 60 mg Extended Release Formulation After a Pretreatment Phase (ISMN-starting Dose: 30 mg) in Stable Coronary Artery Disease (CAD) Patients With or Without Heart Failure Aged 30 to 80 Years - Vericiguat ISOsoRbite Mononitrate Interaction (VISOR) Study

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Placebo; Drug: Vericiguat (BAY1021189); Drug: Isosorbide mononitrate (ISMN)

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charite - Campus Virchow-Klinikum (CVK)
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg Eppendorf (UKE)
  • Baden-Württemberg
    • Bad Krozingen, Baden-Württemberg, Germany, 79189
      • Universitätsherzzentrum Freiburg - Bad Krozingen
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Universitätsklinikum Heidelberg
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53105
      • Medizinische Einrichtungen der Universität Bonn
  • Thüringen
    • Erfurt, Thüringen, Germany, 99084
      • SocraTec R&D GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vericiguat + isosorbite mononitrate; 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).	Drug: Vericiguat (BAY1021189); 2.5 mg/tablet; 5 mg/tablet or 10 mg/tablet; Drug: Isosorbide mononitrate (ISMN); 30 mg/tablet or 60 mg/tablet
Placebo Comparator: Placebo + isosorbite mononitrate; 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).	Drug: Placebo; Matching placebo; Drug: Isosorbide mononitrate (ISMN); 30 mg/tablet or 60 mg/tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	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.	Up to 8 weeks
Heart rate	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.	Up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events	Up to 9 weeks

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Boettcher M, Mikus G, Trenk D, Dungen HD, Donath F, Werner N, Karakas M, Besche N, Schulz-Burck D, Gerrits M, Hung J, Becker C. Vericiguat in combination with isosorbide mononitrate in patients with chronic coronary syndromes: The randomized, phase Ib, VISOR study. Clin Transl Sci. 2022 May;15(5):1204-1214. doi: 10.1111/cts.13238. Epub 2022 Mar 17.

Helpful Links

• Click here to find results for studies related to Bayer products.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2017
• Primary Completion (Actual): February 7, 2018
• Study Completion (Actual): March 23, 2018

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 29, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: 18582; 2016-005178-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No