check_circleStudy Completed

Coronary Artery Disease

Bayer Identifier:

18979

ClinicalTrials.gov Identifier:

NCT03504982

EudraCT Number:

2017-003094-33

EU CT Number:

Not Available
Study to evaluate the QT / QTc interval prolongation potential of vericiguat

Trial purpose

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).

Key Participants Requirements

Sex

All

Age

30 - 80 Years
  • - 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
  • - 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

Trial summary

Enrollment Goal
74
Trial Dates
May 2018 - February 2019
Phase
Phase 1
Could I Receive a placebo
Yes
Products
Verquvo (Vericiguat, BAY1021189)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Universitätsklinikum HeidelbergHeidelberg, 69120, Germany
Completed
Charité - Campus Virchow-Klinikum (CVK)Berlin, 13353, Germany
Completed
SocraTec R&D GmbHErfurt, 99084, Germany
Completed
Universitätsherzzentrum Freiburg - Bad KrozingenBad Krozingen, 79189, Germany
Withdrawn
Universitätsklinikum Hamburg Eppendorf (UKE)Hamburg, 20246, Germany
Completed
Medizinische Einrichtungen der Universität BonnBonn, 53105, Germany
Completed
PAREXEL GmbHBerlin, 14050, Germany
Withdrawn
Universitair Medisch Centrum GroningenGRONINGEN, 9700 RB, Netherlands
Completed
Center for Human Drug ResearchLeiden, 2333 CL, Netherlands
Completed
IMSP Republican Clinical HospitalChisinau, MD2025, Moldova
Withdrawn
St George's University of LondonLondon, SW17 0RE, United Kingdom

Primary Outcome

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

Secondary Outcome

  • Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 2.5 mg vericiguat
    date_rangeTime Frame:
    Baseline and day 1 of vericiguat treatment
  • Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 5 mg vericiguat
    date_rangeTime Frame:
    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
    date_rangeTime Frame:
    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
    date_rangeTime Frame:
    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
    date_rangeTime Frame:
    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
    date_rangeTime Frame:
    Baseline and day 8 of the moxifloxacin treatment period
  • Maximum concentration of vericiguat in plasma after first dose (Cmax)
    date_rangeTime Frame:
    On profile day 1; Timeframe: 0 – 5 hours after dosing
  • Time to maximum concentration of vericiguat in plasma after first dose (tmax)
    date_rangeTime Frame:
    On profile day 1; Timeframe: 0 – 5 hours after dosing
  • Maximum concentration of vericiguat in plasma after multiple doses (Cmax, md)
    date_rangeTime Frame:
    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)
    date_rangeTime Frame:
    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)
    date_rangeTime Frame:
    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)
    date_rangeTime Frame:
    On moxifloxacin profile days (day 8 and 50); Timeframe: 0 – 5 hours after dosing
  • Number of subjects with treatment-emergent adverse events (TEAEs)
    date_rangeTime Frame:
    12 months

Trial design

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)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Basic Science
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
2

Additional Information

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