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

Coronary Artery Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03504982
• Other study ID #: 18979
• Secondary ID: 2017-003094-33
• Status: Completed
• Phase: Phase 1
• Start date: May 17, 2018
• Est. completion date: February 26, 2019

Study information

• Verified date: April 2020
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: February 26, 2019
• Est. primary completion date: November 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Vericiguat (BAY1021189)
A : 2.5 mg vericiguat A*: 2.5 mg vericiguat B : 5 mg vericiguat C : 10 mg vericiguat C*: 10 mg vericiguat
• Moxifloxacin
D: 400 mg moxifloxacin
• Placebo
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

Locations

Country	Name	City	State
Germany	Universitätsherzzentrum Freiburg - Bad Krozingen	Bad Krozingen	Baden-Württemberg
Germany	Charité Campus Virchow-Klinikum (CVK)	Berlin
Germany	PAREXEL GmbH	Berlin
Germany	Medizinische Einrichtungen der Universität Bonn	Bonn	Nordrhein-Westfalen
Germany	SocraTec R&D Clinical Ward	Erfurt	Thüringen
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Moldova, Republic of	IMSP Republican Clinical Hospital	Chisinau
Netherlands	Center for Human Drug Research	Leiden

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

Germany,  Moldova, Republic of,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 2.5 mg vericiguat		Baseline and day 1 of vericiguat treatment
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Time-matched placebo-corrected change from baseline of QTcF after single dose of moxifloxacin		Baseline and day 8 of the moxifloxacin treatment period
Secondary	Maximum concentration of vericiguat in plasma after first dose (Cmax)		On profile day 1; Timeframe: 0 - 5 hours after dosing
Secondary	Time to maximum concentration of vericiguat in plasma after first dose (tmax)		On profile day 1; Timeframe: 0 - 5 hours after dosing
Secondary	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
Secondary	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
Secondary	Maximum concentration of moxifloxacin in plasma after single dose (Cmax)		On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing
Secondary	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
Secondary	Number of subjects with treatment-emergent adverse events (TEAEs)		12 months

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