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

Bayer

Status and phase: Completed; Phase 1

Conditions: Coronary Artery Disease

Treatments: Drug: Vericiguat (BAY1021189); Drug: Placebo; Drug: Moxifloxacin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03504982

2017-003094-33 (EudraCT Number)

18979

Details and patient eligibility

About

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).

Enrollment: 74 patients

Sex: All

Ages: 30 to 80 years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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74 participants in 2 patient groups

Treatment 1

Experimental group

Description:

Treatment sequences: A\*-B-C-D

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: Vericiguat (BAY1021189)

Treatment 2

Experimental group

Description:

Treatment sequences: D-A-B-C\*

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: Vericiguat (BAY1021189)