Vericiguat Drug-drug Interaction With Nitroglycerin in Stable Coronary Artery Disease Patients (VENICE)

Evaluation of the Effect of 0.4 mg Nitroglycerin Spray After Pretreatment With Multiple Once Daily Oral Doses of 2.5 mg, 5 mg and 10 mg Vericiguat (BAY 1021189) Each Given Over 14 ± 3 Days on Safety, Tolerability and Blood Pressure in a Multi-center, Randomized, Placebo-controlled, Double-blind Group Comparison Study in Stable Coronary Artery Disease (CAD) Patients Aged 30 to 80 Years

This study is intended to investigate the effect of nitroglycerin on vericiguat in patients with stable coronary artery disease (CAD). Nitroglycerin is the standard therapy to treat acute crisis of angina. Thus there is a high likelihood of co-administration of both drugs in the target indication of vericiguat, worsening heart failure (HF). Therefore, it is important to investigate the safety and tolerability of vericiguat and nitroglycerin, which may be used as unprescribed on-demand treatment by patients with acute episodes of angina pectoris.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
  • Hamburg, Germany, 20251
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53105
    • Wuppertal, Nordrhein-Westfalen, Germany, 42283
  • Thüringen
    • Erfurt, Thüringen, Germany, 99084

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
• Body mass index (BMI): above/equal 18.0 and below/equal 36.0 kg / m²
• Female subjects must be of non-childbearing potential

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
• 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 or patients with stroke at more than 3 months prior with significant residual neurologic involvement
• Insulin dependent diabetes mellitus
• Clinically relevant cardiac ischemia
• Clinical significant persistent ischemia
• Atrial fibrillation, pacemaker, defibrillator, atrial ventricular (AV)-block II and III
• Systolic blood pressure below 110 or above 160 mmHg
• Diastolic blood pressure above 100 mmHg
• Heart rate below 50 or above 100 beats / min
• Estimated glomerular filtration rate < 30 mL/min/1.73m2

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 + Nitroglycerin; Co-administration of vericiguat and nitroglycerin	Drug: Vericiguat (BAY1021189); Vericiguat up-titration from 2.5 mg to 10 mg in an interval of 14 +/- 3 days: 2.5 mg vericiguat for 14 +/-3 days given as 2 x 1.25 mg tablets followed by 5 mg vericiguat for 14 +/-3 days given as 1 x 5 mg tablet followed by 10 mg vericiguat for 14 +/-3 days given as 2 x 5 mg tablets; Drug: Nitroglycerin; 0.4 mg nitroglycerin spray administered at 2.5 hours before treatment (vericiguat [trough] or placebo) on day 12, day 26 and day 40 at 4 hours after treatment (vericiguat [peak] or placebo) on day 13, day 27 and day 41
Placebo Comparator: Placebo + Nitroglycerin; Aministration of matching placebo and nitroglycerin.	Drug: Nitroglycerin; 0.4 mg nitroglycerin spray administered at 2.5 hours before treatment (vericiguat [trough] or placebo) on day 12, day 26 and day 40 at 4 hours after treatment (vericiguat [peak] or placebo) on day 13, day 27 and day 41; Drug: Placebo; Placebo for 14 +/-3 days given as 1 or 2 tablets [o.d.].

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as measure of safety and tolerability	approximately 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Regular measurement of blood pressure (mmHg) in supine, sitting and standing position.	approximately 1 year
Heart rate	Regular measurement of heart rate (bpm) in supine, sitting and standing position.	approximately 1 year

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2015
• Primary Completion (Actual): May 18, 2016
• Study Completion (Actual): August 11, 2016

Study Registration Dates

• First Submitted: November 11, 2015
• First Submitted That Met QC Criteria: November 26, 2015
• First Posted (Estimate): December 1, 2015

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; Vasodilator Agents; Nitroglycerin
• Other Study ID Numbers: 17849; 2015-001444-11 (EudraCT Number)