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

• Status: Completed
• Trial end date: 2019-02-26
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bayer
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Fluoroquinolones; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination

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