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

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ClinicalTrials.gov Identifier: NCT03504982
Recruitment Status : Completed
First Posted : April 20, 2018
Last Update Posted : March 12, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Bayer

Brief Summary:
The objective of this study is to evaluate the effect of multiple doses of vericiguat on the QTc interval in patients with stable CAD (coronary artery disease).

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Vericiguat (BAY1021189) Drug: Moxifloxacin Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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)
Actual Study Start Date : May 17, 2018
Actual Primary Completion Date : November 29, 2018
Actual Study Completion Date : February 26, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment 1
Treatment sequences: A*-B-C-D
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

Drug: Moxifloxacin
D: 400 mg moxifloxacin

Drug: 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

Experimental: Treatment 2
Treatment sequences: D-A-B-C*
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

Drug: Moxifloxacin
D: 400 mg moxifloxacin

Drug: 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




Primary Outcome Measures :
  1. 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 Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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) ]
  5. 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) ]
  6. 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 ]
  7. Cmax of vericiguat [ Time Frame: On profile day 1; Timeframe: 0 - 5 hours after dosing ]
    Cmax: maximum plasma concentration

  8. tmax of vericiguat [ Time Frame: On profile day 1; Timeframe: 0 - 5 hours after dosing ]
    tmax: time to reach Cmax

  9. Cmax, ss of vericiguat [ Time Frame: On profile days: 8, 14, 15, 28, 29, 42, 43, 50 and 56; Timeframe: 0 - 5 hours after dosing ]
    Cmax, ss: maximum observed drug concentration at steady state during a dosage interval

  10. tmax,ss of vericiguat [ Time Frame: On profile days: 1, 8, 14, 15, 28, 29, 42, 43, 50 and 56; Timeframe: 0 - 5 hours after dosing ]
    tmax,ss: time to reach Cmax at steady state

  11. Cmax of Moxifloxacin [ Time Frame: On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing ]
  12. tmax of Moxifloxacin [ Time Frame: On moxifloxacin profile days (day 8 and 50); Timeframe: 0 - 5 hours after dosing ]
  13. The number of subjects with TEAEs (treatment-emergent adverse events) [ Time Frame: 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03504982


Locations
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Germany
Universitätsherzzentrum Freiburg - Bad Krozingen
Bad Krozingen, Baden-Württemberg, Germany, 79189
Universitätsklinikum Heidelberg
Heidelberg, Baden-Württemberg, Germany, 69120
Medizinische Einrichtungen der Universität Bonn
Bonn, Nordrhein-Westfalen, Germany, 53105
SocraTec R&D Clinical Ward
Erfurt, Thüringen, Germany, 99084
Charité Campus Virchow-Klinikum (CVK)
Berlin, Germany, 13353
PAREXEL GmbH
Berlin, Germany, 14050
Moldova, Republic of
IMSP Republican Clinical Hospital
Chisinau, Moldova, Republic of, MD2025
Netherlands
Center for Human Drug Research
Leiden, Netherlands, 2333 CL
Sponsors and Collaborators
Bayer
Merck Sharp & Dohme Corp.

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03504982     History of Changes
Other Study ID Numbers: 18979
2017-003094-33 ( EudraCT Number )
First Posted: April 20, 2018    Key Record Dates
Last Update Posted: March 12, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Vericiguat
Stable CAD
QT/QTc

Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs