Study to Evaluate the QT / QTc Interval Prolongation Potential of Vericiguat

Study to Clinically Evaluate the QT/QTc Interval Prolongation Potential of Vericiguat in Patients With Stable Coronary Artery Disease in a 2-arm, Placebo-controlled, Randomized, Double-blind, Double-dummy Design Including a Vericiguat Multiple-dose Part With Fixed up Titration Periods and Moxifloxacin as Positive Control (for Assay Sensitivity Testing, Nested Into the Placebo Treatment)

The primary objective of this study was to investigate whether there is a clinically meaningful effect on QTc change from baseline relative to placebo after administration of 10 mg at steady state in patients with stable CAD (coronary artery disease).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charité Campus Virchow-Klinikum (CVK)
  • Berlin, Germany, 14050
    • PAREXEL GmbH
  • 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 Clinical Ward
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD2025
    • IMSP Republican Clinical Hospital
• Netherlands
  • Leiden, Netherlands, 2333 CL
    • Center for Human Drug Research

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 (coronary artery disease) defined by:

  • clinically stable for at least 3 months
  • coronary artery stenosis in any of the 3 main coronary vessels
  • or history of myocardial infarction
• Sinus rhythm at screening
• Interpretable echocardiographic images
• Age: 30 to 80 years
• Body mass index (BMI): above/equal 18.0 and below/equal 36.0 kg/m²

Exclusion Criteria:

• Ejection fraction (EF) below 30% at screening
• Progressive angina with symptoms of worsening of angina within the <3 month
• History of recent myocardial infarction or unstable Angina
• Documented current relevant coronary stenosis ≥90% in any of the main 3 coronary vessels without bypass graft
• Symptomatic carotid stenosis, or transient ischemic attack or stroke within 3 months or patients with stroke at more than 3 months
• Insulin dependent diabetes mellitus
• Clinically significant and persisting cardiac ischemia
• Atrial fibrillation, pacemaker, defibrillator, second and third degree atrial-ventricular (AV) block
• Known clinically relevant ventricular arrhythmias
• Clinically relevant heart failure with reduced left ventricular ejection fraction
• Significant valvular heart disease with moderate or severe aortic stenosis or any other significant stenosis; any other moderate or severe valvular failures
• Valve replacement
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Previous or imminent cardiac transplantation
• Known long QT syndrome or prolongation of the QT interval with ongoing proarrhythmic conditions
• Co-medication with drugs known to have QT prolonging effect
• Intolerance of fluoroquinolones, including moxifloxacin
• History of serious adverse effects e.g. tendinitis and tendon rupture, arthralgia and effects on the peripheral and central nervous system while taking fluoroquinolones including moxifloxacin
• History of tendon diseases or tendon injury caused by quinolones
• Treatment with fluoroquinolones, including moxifloxacin during the last 2 weeks
• Treatment with organic nitrates during the last 3 months
• Treatment with riociguat during the last 3 months
• Treatment with phosphodiesterase (PDE)-5 inhibitors during the last 14 days
• Systolic blood pressure below 110 or above 160 mmHg at screening visit
• Diastolic blood pressure below 50 or above 100 mmHg at screening visit
• Heart rate below 50 or above 100 beats/min (taken from ECG measurement) at first screening visit
• Estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73m*2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment 1; Treatment sequences: A*-B-C-D	Drug: Vericiguat (BAY1021189); A : 2.5 mg vericiguat A*: 2.5 mg vericiguat B : 5 mg vericiguat C : 10 mg vericiguat C*: 10 mg vericiguat; Drug: Moxifloxacin; D: 400 mg moxifloxacin; Drug: Placebo; A : vericiguat placebo 10 mg A*: vericiguat placebo 10 mg + moxifloxacin placebo B : vericiguat placebo 10 mg C : vericiguat placebo 2.5 mg C*: vericiguat placebo 2.5 mg + moxifloxacin placebo D : vericiguat placebo 2.5 mg + vericiguat placebo 10 mg
Experimental: Treatment 2; Treatment sequences: D-A-B-C*	Drug: Vericiguat (BAY1021189); A : 2.5 mg vericiguat A*: 2.5 mg vericiguat B : 5 mg vericiguat C : 10 mg vericiguat C*: 10 mg vericiguat; Drug: Moxifloxacin; D: 400 mg moxifloxacin; Drug: Placebo; A : vericiguat placebo 10 mg A*: vericiguat placebo 10 mg + moxifloxacin placebo B : vericiguat placebo 10 mg C : vericiguat placebo 2.5 mg C*: vericiguat placebo 2.5 mg + moxifloxacin placebo D : vericiguat placebo 2.5 mg + vericiguat placebo 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time-matched placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) after 10 mg vericiguat at steady state.	Baseline, day 56 (steady state 10 mg) of vericiguat treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 2.5 mg vericiguat	Baseline and day 1 of vericiguat treatment
Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 5 mg vericiguat	Baseline and day 15 (+/- 3 days) of vericiguat treatment
Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 10 mg vericiguat	Baseline and day 29 (+/- 3 days) of vericiguat treatment
Time-matched placebo-corrected change from baseline of QTcF after 2.5 mg vericiguat at steady state	Baseline and day 14 (+/- 3 days) of vericiguat treatment (steady state 2.5 mg)
Time-matched placebo-corrected change from baseline of QTcF after 5 mg vericiguat at steady state	Baseline and day 28 (+/- 3 days) of vericiguat treatment (steady state 5 mg)
Time-matched placebo-corrected change from baseline of QTcF after single dose of moxifloxacin	Baseline and day 8 of the moxifloxacin treatment period
Maximum concentration of vericiguat in plasma after first dose (Cmax)	On profile day 1; Timeframe: 0 - 5 hours after dosing
Time to maximum concentration of vericiguat in plasma after first dose (tmax)	On profile day 1; Timeframe: 0 - 5 hours after dosing
Maximum concentration of vericiguat in plasma after multiple doses (Cmax, md)	On profile days: 8, 14, 15, 28, 29, 42, 43, 50 and 56; Timeframe: 0 - 5 hours after dosing
Time to maximum concentration of vericiguat in plasma after multiple doses (tmax, md)	On profile days: 1, 8, 14, 15, 28, 29, 42, 43, 50 and 56; Timeframe: 0 - 5 hours after dosing
Maximum concentration of moxifloxacin in plasma after single dose (Cmax)	On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing
Time to maximum concentration of moxifloxacin in plasma after single dose (tmax)	On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing
Number of subjects with treatment-emergent adverse events (TEAEs)	12 months

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): May 17, 2018
• Primary Completion (Actual): November 29, 2018
• Study Completion (Actual): February 26, 2019

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (Actual): April 20, 2018

Study Record Updates

• Last Update Posted (Actual): April 17, 2020
• Last Update Submitted That Met QC Criteria: April 16, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: QT/QTc; Vericiguat; Stable CAD
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: 18979; 2017-003094-33 (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