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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03504982
• Date of registration: 13/04/2018
• Prospective Registration: Yes
• Primary sponsor: Bayer
• Public title: Study to Evaluate the QT / QTc Interval Prolongation Potential of Vericiguat
• Scientific 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)
• Date of first enrolment: May 17, 2018
• Target sample size: 74
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03504982
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

Germany, Moldova, Republic of, Netherlands, United Kingdom

Key inclusion & exclusion 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



Age minimum: 30 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Coronary Artery Disease

Intervention(s)

Drug: Moxifloxacin

Drug: Vericiguat (BAY1021189)

Drug: Placebo

Primary Outcome(s)

Time-matched placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) after 10 mg vericiguat at steady state. [Time Frame: Baseline, day 56 (steady state 10 mg) of vericiguat treatment]

Secondary Outcome(s)

Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 10 mg vericiguat [Time Frame: Baseline and day 29 (+/- 3 days) of vericiguat treatment]

Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 5 mg vericiguat [Time Frame: Baseline and day 15 (+/- 3 days) of vericiguat treatment]

Time-matched placebo-corrected change from baseline of QTcF after single dose of moxifloxacin [Time Frame: Baseline and day 8 of the moxifloxacin treatment period]

Time-matched placebo-corrected change from baseline of QTcF after 2.5 mg vericiguat at steady state [Time Frame: Baseline and day 14 (+/- 3 days) of vericiguat treatment (steady state 2.5 mg)]

Time to maximum concentration of vericiguat in plasma after multiple doses (tmax, md) [Time Frame: 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) [Time Frame: On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing]

Time-matched placebo-corrected change from baseline of QTcF after 1st dose of 2.5 mg vericiguat [Time Frame: Baseline and day 1 of vericiguat treatment]

Maximum concentration of vericiguat in plasma after first dose (Cmax) [Time Frame: On profile day 1; Timeframe: 0 - 5 hours after dosing]

Time-matched placebo-corrected change from baseline of QTcF after 5 mg vericiguat at steady state [Time Frame: Baseline and day 28 (+/- 3 days) of vericiguat treatment (steady state 5 mg)]

Maximum concentration of vericiguat in plasma after multiple doses (Cmax, md) [Time Frame: On profile days: 8, 14, 15, 28, 29, 42, 43, 50 and 56; Timeframe: 0 - 5 hours after dosing]

Time to maximum concentration of moxifloxacin in plasma after single dose (tmax) [Time Frame: On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing]

Time to maximum concentration of vericiguat in plasma after first dose (tmax) [Time Frame: On profile day 1; Timeframe: 0 - 5 hours after dosing]

Number of subjects with treatment-emergent adverse events (TEAEs) [Time Frame: 12 months]

Secondary ID(s)

18979

2017-003094-33

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck Sharp & Dohme Corp.