Study to Evaluate the QT / QTc Interval Prolongation Potential of Vericiguat
Phase 1
Completed
- Conditions
- Coronary Artery Disease
- Interventions
- Registration Number
- NCT03504982
- Lead Sponsor
- Bayer
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 74
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment 1 Vericiguat (BAY1021189) Treatment sequences: A\*-B-C-D Treatment 1 Placebo Treatment sequences: A\*-B-C-D Treatment 2 Vericiguat (BAY1021189) Treatment sequences: D-A-B-C\* Treatment 2 Moxifloxacin Treatment sequences: D-A-B-C\* Treatment 2 Placebo Treatment sequences: D-A-B-C\* Treatment 1 Moxifloxacin Treatment sequences: A\*-B-C-D
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Trial Locations
- Locations (8)
Universitätsherzzentrum Freiburg - Bad Krozingen
🇩🇪Bad Krozingen, Baden-Württemberg, Germany
Center for Human Drug Research
🇳🇱Leiden, Netherlands
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Medizinische Einrichtungen der Universität Bonn
🇩🇪Bonn, Nordrhein-Westfalen, Germany
PAREXEL GmbH
🇩🇪Berlin, Germany
Charité Campus Virchow-Klinikum (CVK)
🇩🇪Berlin, Germany
IMSP Republican Clinical Hospital
🇲🇩Chisinau, Moldova, Republic of
SocraTec R&D Clinical Ward
🇩🇪Erfurt, Thüringen, Germany