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

Primary Purpose

Coronary Artery Disease

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

Vericiguat (BAY1021189)

Placebo

Isosorbide mononitrate (ISMN)

About this trial

This is an interventional treatment trial for Coronary Artery Disease

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Universitätsherzzentrum Freiburg - Bad Krozingen
Universitätsklinikum Heidelberg
Medizinische Einrichtungen der Universität Bonn
SocraTec R&D GmbH
Charité - Campus Virchow-Klinikum (CVK)
Universitätsklinikum Hamburg Eppendorf (UKE)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Vericiguat + isosorbite mononitrate

Placebo + isosorbite mononitrate

Arm 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).

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).

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Number of participants with adverse events

Full Information

NCT ID

NCT03255512

First Posted

August 3, 2017

Last Updated

December 9, 2021

Sponsor

Bayer

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03255512

Brief Title

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

Acronym

VISOR

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

August 17, 2017 (Actual)

Primary Completion Date

February 7, 2018 (Actual)

Study Completion Date

March 23, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronary Artery Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

41 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vericiguat + isosorbite mononitrate

Arm Type

Experimental

Arm Description

Arm Title

Placebo + isosorbite mononitrate

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Vericiguat (BAY1021189)

Intervention Description

2.5 mg/tablet; 5 mg/tablet or 10 mg/tablet

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo

Intervention Type

Drug

Intervention Name(s)

Isosorbide mononitrate (ISMN)

Intervention Description

30 mg/tablet or 60 mg/tablet

Primary Outcome Measure Information:

Title

Blood pressure

Description

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.

Time Frame

Up to 8 weeks

Title

Heart rate

Description

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.

Time Frame

Up to 8 weeks

Secondary Outcome Measure Information:

Title

Number of participants with adverse events

Time Frame

Up to 9 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

Facility Name

Universitätsherzzentrum Freiburg - Bad Krozingen

City

Bad Krozingen

State/Province

Baden-Württemberg

ZIP/Postal Code

79189

Country

Germany

Facility Name

Universitätsklinikum Heidelberg

City

Heidelberg

State/Province

Baden-Württemberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Medizinische Einrichtungen der Universität Bonn

City

Bonn

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

53105

Country

Germany

Facility Name

SocraTec R&D GmbH

City

Erfurt

State/Province

Thüringen

ZIP/Postal Code

99084

Country

Germany

Facility Name

Charité - Campus Virchow-Klinikum (CVK)

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Universitätsklinikum Hamburg Eppendorf (UKE)

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

35299288

Citation

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.

Results Reference

derived

Links:

URL

http://clinicaltrials.bayer.com/

Description

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

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

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