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

NCT ID: NCT03255512

Last Updated: 2021-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-17
• Study Completion Date: 2018-03-23

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Vericiguat (BAY1021189)

Intervention Type: DRUG

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

Isosorbide mononitrate (ISMN)

Intervention Type: DRUG

30 mg/tablet or 60 mg/tablet

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo

Isosorbide mononitrate (ISMN)

Intervention Type: DRUG

30 mg/tablet or 60 mg/tablet

Interventions

Vericiguat (BAY1021189)

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

Intervention Type: DRUG

Placebo

Matching placebo

Intervention Type: DRUG

Isosorbide mononitrate (ISMN)

30 mg/tablet or 60 mg/tablet

Intervention Type: DRUG

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Universitätsherzzentrum Freiburg - Bad Krozingen

Bad Krozingen, Baden-Wurttemberg, Germany

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Medizinische Einrichtungen der Universität Bonn

Bonn, North Rhine-Westphalia, Germany

SocraTec R&D GmbH

Erfurt, Thuringia, Germany

Charité - Campus Virchow-Klinikum (CVK)

Berlin, , Germany

Universitätsklinikum Hamburg Eppendorf (UKE)

Hamburg, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 35299288 (View on PubMed)

Related Links

http://clinicaltrials.bayer.com/

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

Other Identifiers

2016-005178-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

18582

Identifier Type: -

Identifier Source: org_study_id