Coronary Artery Disease
Conditions
Keywords
Vericiguat, Stable CAD, QT/QTc
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).
Interventions
A : 2.5 mg vericiguat A\*: 2.5 mg vericiguat B : 5 mg vericiguat C : 10 mg vericiguat C\*: 10 mg vericiguat
DRUGMoxifloxacin
D: 400 mg moxifloxacin
DRUGPlacebo
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
Sponsors
Merck Sharp & Dohme LLC
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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-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 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 |
| 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 |
Countries
Germany, Moldova, Netherlands
Outcome results
None listed