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

Primary Purpose

Coronary Artery Disease

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Vericiguat (BAY1021189)
Moxifloxacin
Placebo
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Coronary Artery Disease focused on measuring Vericiguat, Stable CAD, QT/QTc

Eligibility Criteria

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

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

Sites / Locations

  • Universitätsherzzentrum Freiburg - Bad Krozingen
  • Universitätsklinikum Heidelberg
  • Medizinische Einrichtungen der Universität Bonn
  • SocraTec R&D Clinical Ward
  • Charité Campus Virchow-Klinikum (CVK)
  • PAREXEL GmbH
  • IMSP Republican Clinical Hospital
  • Center for Human Drug Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Treatment 1

Treatment 2

Arm Description

Treatment sequences: A*-B-C-D

Treatment sequences: D-A-B-C*

Outcomes

Primary Outcome Measures

Time-matched placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) after 10 mg vericiguat at steady state.

Secondary Outcome Measures

Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 2.5 mg vericiguat
Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 5 mg vericiguat
Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 10 mg vericiguat
Time-matched placebo-corrected change from baseline of QTcF after 2.5 mg vericiguat at steady state
Time-matched placebo-corrected change from baseline of QTcF after 5 mg vericiguat at steady state
Time-matched placebo-corrected change from baseline of QTcF after single dose of moxifloxacin
Maximum concentration of vericiguat in plasma after first dose (Cmax)
Time to maximum concentration of vericiguat in plasma after first dose (tmax)
Maximum concentration of vericiguat in plasma after multiple doses (Cmax, md)
Time to maximum concentration of vericiguat in plasma after multiple doses (tmax, md)
Maximum concentration of moxifloxacin in plasma after single dose (Cmax)
Time to maximum concentration of moxifloxacin in plasma after single dose (tmax)
Number of subjects with treatment-emergent adverse events (TEAEs)

Full Information

First Posted
April 13, 2018
Last Updated
April 16, 2020
Sponsor
Bayer
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03504982
Brief Title
Study to Evaluate the QT / QTc Interval Prolongation Potential of Vericiguat
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
May 17, 2018 (Actual)
Primary Completion Date
November 29, 2018 (Actual)
Study Completion Date
February 26, 2019 (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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
Vericiguat, Stable CAD, QT/QTc

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment 1
Arm Type
Experimental
Arm Description
Treatment sequences: A*-B-C-D
Arm Title
Treatment 2
Arm Type
Experimental
Arm Description
Treatment sequences: D-A-B-C*
Intervention Type
Drug
Intervention Name(s)
Vericiguat (BAY1021189)
Intervention Description
A : 2.5 mg vericiguat A*: 2.5 mg vericiguat B : 5 mg vericiguat C : 10 mg vericiguat C*: 10 mg vericiguat
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin
Intervention Description
D: 400 mg moxifloxacin
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Time-matched placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) after 10 mg vericiguat at steady state.
Time Frame
Baseline, day 56 (steady state 10 mg) of vericiguat treatment
Secondary Outcome Measure Information:
Title
Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 2.5 mg vericiguat
Time Frame
Baseline and day 1 of vericiguat treatment
Title
Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 5 mg vericiguat
Time Frame
Baseline and day 15 (+/- 3 days) of vericiguat treatment
Title
Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 10 mg vericiguat
Time Frame
Baseline and day 29 (+/- 3 days) of vericiguat treatment
Title
Time-matched placebo-corrected change from baseline of QTcF after 2.5 mg vericiguat at steady state
Time Frame
Baseline and day 14 (+/- 3 days) of vericiguat treatment (steady state 2.5 mg)
Title
Time-matched placebo-corrected change from baseline of QTcF after 5 mg vericiguat at steady state
Time Frame
Baseline and day 28 (+/- 3 days) of vericiguat treatment (steady state 5 mg)
Title
Time-matched placebo-corrected change from baseline of QTcF after single dose of moxifloxacin
Time Frame
Baseline and day 8 of the moxifloxacin treatment period
Title
Maximum concentration of vericiguat in plasma after first dose (Cmax)
Time Frame
On profile day 1; Timeframe: 0 - 5 hours after dosing
Title
Time to maximum concentration of vericiguat in plasma after first dose (tmax)
Time Frame
On profile day 1; Timeframe: 0 - 5 hours after dosing
Title
Maximum concentration of vericiguat in plasma after multiple doses (Cmax, md)
Time Frame
On profile days: 8, 14, 15, 28, 29, 42, 43, 50 and 56; Timeframe: 0 - 5 hours after dosing
Title
Time to maximum concentration of vericiguat in plasma after multiple doses (tmax, md)
Time Frame
On profile days: 1, 8, 14, 15, 28, 29, 42, 43, 50 and 56; Timeframe: 0 - 5 hours after dosing
Title
Maximum concentration of moxifloxacin in plasma after single dose (Cmax)
Time Frame
On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing
Title
Time to maximum concentration of moxifloxacin in plasma after single dose (tmax)
Time Frame
On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing
Title
Number of subjects with treatment-emergent adverse events (TEAEs)
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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 Clinical Ward
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
PAREXEL GmbH
City
Berlin
ZIP/Postal Code
14050
Country
Germany
Facility Name
IMSP Republican Clinical Hospital
City
Chisinau
ZIP/Postal Code
MD2025
Country
Moldova, Republic of
Facility Name
Center for Human Drug Research
City
Leiden
ZIP/Postal Code
2333 CL
Country
Netherlands

12. IPD Sharing Statement

Links:
URL
https://clinicaltrials.bayer.com/
Description
Click here to find results for studies related to Bayer products.

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

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