Study 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

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

Trial summary

Enrollment Goal

Trial Dates

May 2018 - February 2019

Phase

Phase 1

Could I Receive a placebo

Yes

Products

Verquvo (Vericiguat, BAY1021189)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	Universitätsklinikum Heidelberg	Heidelberg, 69120, Germany
Completed	Charité - Campus Virchow-Klinikum (CVK)	Berlin, 13353, Germany
Completed	SocraTec R&D GmbH	Erfurt, 99084, Germany
Completed	Universitätsherzzentrum Freiburg - Bad Krozingen	Bad Krozingen, 79189, Germany
Withdrawn	Universitätsklinikum Hamburg Eppendorf (UKE)	Hamburg, 20246, Germany
Completed	Medizinische Einrichtungen der Universität Bonn	Bonn, 53105, Germany
Completed	PAREXEL GmbH	Berlin, 14050, Germany
Withdrawn	Universitair Medisch Centrum Groningen	GRONINGEN, 9700 RB, Netherlands
Completed	Center for Human Drug Research	Leiden, 2333 CL, Netherlands
Completed	IMSP Republican Clinical Hospital	Chisinau, MD2025, Moldova
Withdrawn	St George's University of London	London, 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.
Time 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
Time Frame:
Baseline and day 1 of vericiguat treatment
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
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
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)
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)
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
Maximum concentration of vericiguat in plasma after first dose (Cmax)
Time Frame:
On profile day 1; Timeframe: 0 – 5 hours after dosing
Time to maximum concentration of vericiguat in plasma after first dose (tmax)
Time Frame:
On profile day 1; Timeframe: 0 – 5 hours after dosing
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
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
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
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
Number of subjects with treatment-emergent adverse events (TEAEs)
Time 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

Additional Information

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