NCT03255512

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
41

participants targeted

Target at P50-P75 for phase_1 coronary-artery-disease

Timeline
Completed

Started Aug 2017

Shorter than P25 for phase_1 coronary-artery-disease

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 3, 2017

Completed
14 days until next milestone

Study Start

First participant enrolled

August 17, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 21, 2017

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 7, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

March 23, 2018

Completed
Last Updated

December 29, 2021

Status Verified

December 1, 2021

Enrollment Period

6 months

First QC Date

August 3, 2017

Last Update Submit

December 9, 2021

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (1)

  • Number of participants with adverse events

    Up to 9 weeks

Study Arms (2)

Vericiguat + isosorbite mononitrate

EXPERIMENTAL

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)Drug: Isosorbide mononitrate (ISMN)

Placebo + isosorbite mononitrate

PLACEBO COMPARATOR

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: PlaceboDrug: Isosorbide mononitrate (ISMN)

Interventions

Vericiguat (BAY1021189)DRUG

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

Vericiguat + isosorbite mononitrate
PlaceboDRUG

Matching placebo

Placebo + isosorbite mononitrate
Isosorbide mononitrate (ISMN)DRUG

30 mg/tablet or 60 mg/tablet

Placebo + isosorbite mononitrateVericiguat + isosorbite mononitrate

Eligibility Criteria

Age30 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Universitätsherzzentrum Freiburg - Bad Krozingen

Bad Krozingen, Baden-Wurttemberg, 79189, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Medizinische Einrichtungen der Universität Bonn

Bonn, North Rhine-Westphalia, 53105, Germany

Location

SocraTec R&D GmbH

Erfurt, Thuringia, 99084, Germany

Location

Charité - Campus Virchow-Klinikum (CVK)

Berlin, 13353, Germany

Location

Universitätsklinikum Hamburg Eppendorf (UKE)

Hamburg, 20246, Germany

Location

Related Publications (1)

  • 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.

    PMID: 35299288DERIVED

Related Links

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

vericiguatisosorbide-5-mononitrate

Condition Hierarchy (Ancestors)

Coronary DiseaseMyocardial IschemiaHeart DiseasesCardiovascular DiseasesArteriosclerosisArterial Occlusive DiseasesVascular Diseases

Study Officials

  • Bayer Study Director

    Bayer

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 3, 2017

First Posted

August 21, 2017

Study Start

August 17, 2017

Primary Completion

February 7, 2018

Study Completion

March 23, 2018

Last Updated

December 29, 2021

Record last verified: 2021-12

Locations

DE(6)