Vericiguat Drug-drug Interaction Study With Isosorbite Mononitrate in Stable Coronary Artery Disease Patients

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: Vericiguat (BAY1021189) + isosorbite mononitrate Other Names Drug: Placebo + isosorbite mononitrate (ISMN) Other Names	Phase 1

Tracking Information

First Submitted Date	August 03, 2017
Last Update Posted Date	February 12, 2018
Actual Start Date	August 17, 2017
Anticipated Completion Date	March 06, 2018
Actual Primary Completion Date	February 06, 2018
Results First Submitted Date	N/A
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• Blood pressure [Time Frame: Up to 8 weeks]

  Regular measurements of blood pressure after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.

• Heart rate [Time Frame: Up to 8 weeks]

  Regular measurements heart rate after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.

Original Primary Outcome Measures

Current Secondary Outcome Measures

• Number of participants with adverse events [Time Frame: Up to 9 weeks]

Original Secondary Outcome Measures

Study Design

Brief Title	Vericiguat Drug-drug Interaction Study With Isosorbite Mononitrate in Stable Coronary Artery Disease Patients
Official Title	Multi-center, Randomized, Placebo-controlled, Double-blind Group Comparison Study to Investigate Safety, Tolerability and Blood Pressure of 2.5 mg, 5.0 mg and 10 mg Vericiguat Each Given Over 14 ± 3 Days Together With Isosorbite Mononitrate (ISMN) 60 mg Extended Release Formulation After a Pretreatment Phase (ISMN-starting Dose: 30 mg) in Stable Coronary Artery Disease (CAD) Patients With or Without Heart Failure Aged 30 to 80 Years - Vericiguat ISOsoRbite Mononitrate Interaction (VISOR) Study
Brief Summary	This study is intended to investigate the pharmacodynamic drug-drug interaction as well as the safety and tolerability of isosorbite mononitrate and vericiguat in patients with stable coronary artery disease.
Detailed Description
Study Type	Interventional
Study Phase	Phase 1
Estimated Enrollment	41
Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Conditions	Coronary Artery Disease
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Drug: Vericiguat (BAY1021189) + isosorbite mononitrate ISMN up-titration with 30 mg / 60 mg, about 7 days each, prior to start of vericiguat administration Starting dose of 2.5 mg taken orally once daily with food, on a background of standard of care. Dose will be up-titrated to 5 mg and to 10 mg: 2.5 mg vericiguat for about 14 days followed by 5 mg vericiguat for about 14 days followed by 10 mg vericiguat for about 14 days 60 mg ISMN od on each day of vericiguat administration, taken 1 hour prior to vericiguat (in-house days) or together with vericiguat (out-patient days) Other Names Drug: Placebo + isosorbite mononitrate (ISMN) ISMN up-titration with 30 mg / 60 mg, about 7 days each, prior to start of placebo administration Placebo for about 14 days, once daily 60 mg ISMN od on each day of placebo administration, taken 1 hour prior to placebo (in-house days) or together with placebo (out-patient days) Other Names
Study Groups/Cohorts	Vericiguat + isosorbite mononitrate Co-administration of vericiguat and isosorbite mononitrate. Placebo + isosorbite mononitrate Administration of (vericiguat) matching placebo and isosorbite mononitrate.
Study Arms	Placebo Comparator Placebo + isosorbite mononitrate Administration of (vericiguat) matching placebo and isosorbite mononitrate. Drug : Placebo + isosorbite mononitrate (ISMN) ISMN up-titration with 30 mg / 60 mg, about 7 days each, prior to start of placebo administration Placebo for about 14 days, once daily 60 mg ISMN od on each day of placebo administration, taken 1 hour prior to placebo (in-house days) or together with placebo (out-patient days) Experimental Vericiguat + isosorbite mononitrate Co-administration of vericiguat and isosorbite mononitrate. Drug : Vericiguat (BAY1021189) + isosorbite mononitrate ISMN up-titration with 30 mg / 60 mg, about 7 days each, prior to start of vericiguat administration Starting dose of 2.5 mg taken orally once daily with food, on a background of standard of care. Dose will be up-titrated to 5 mg and to 10 mg: 2.5 mg vericiguat for about 14 days followed by 5 mg vericiguat for about 14 days followed by 10 mg vericiguat for about 14 days 60 mg ISMN od on each day of vericiguat administration, taken 1 hour prior to vericiguat (in-house days) or together with vericiguat (out-patient days)

Arm	Intervention/Treatment
Placebo Comparator Placebo + isosorbite mononitrate Administration of (vericiguat) matching placebo and isosorbite mononitrate.	Drug : Placebo + isosorbite mononitrate (ISMN) ISMN up-titration with 30 mg / 60 mg, about 7 days each, prior to start of placebo administration Placebo for about 14 days, once daily 60 mg ISMN od on each day of placebo administration, taken 1 hour prior to placebo (in-house days) or together with placebo (out-patient days)
Experimental Vericiguat + isosorbite mononitrate Co-administration of vericiguat and isosorbite mononitrate.	Drug : Vericiguat (BAY1021189) + isosorbite mononitrate ISMN up-titration with 30 mg / 60 mg, about 7 days each, prior to start of vericiguat administration Starting dose of 2.5 mg taken orally once daily with food, on a background of standard of care. Dose will be up-titrated to 5 mg and to 10 mg: 2.5 mg vericiguat for about 14 days followed by 5 mg vericiguat for about 14 days followed by 10 mg vericiguat for about 14 days 60 mg ISMN od on each day of vericiguat administration, taken 1 hour prior to vericiguat (in-house days) or together with vericiguat (out-patient days)

Recruitment Information

Recruitment Status:	Active, not recruiting
Enrollment	41
Completion Date	March 06, 2018
Eligibility Criteria:	Inclusion Criteria: Patients with stable CAD defined by - coronary artery stenosis in any of the 3 main coronary vessels > 50% documented by coronary angiography within last 36 months - or history of myocardial infarction - Age: 30 to 80 years (inclusive) at the first screening examination - Body mass index (BMI): above/equal 18.0 and below/equal 36.0 kg / m² Exclusion Criteria: - Intervention e.g. revascularization by percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) during the last 3 months - Progressive angina with symptoms of worsening of angina within the < 3 months prior to the first screening examination - History of recent (< 6 months prior to the first screening examination) myocardial infarction or unstable angina - Symptomatic carotid stenosis, or transient ischemic attack or stroke within 3 months prior to the first screening examination or patients with stroke at more than 3 months prior to the first screening examination with significant residual neurologic involvement - Insulin dependent diabetes mellitus - Clinically relevant cardiac ischemia at screening - Clinical significant persistent ischemia, which should be ruled out by clinical judgment of the investigator, based on medical history, available clinical data e.g. past angiograms or preexisting or current exercise testing with any imaging technique (e.g. dobutamine stress echocardiography, adenosine or dobutamine stress cardiac magnetic resonance imaging (CMR), scinthigraphy or exercise ECG) - Atrial fibrillation, pacemaker, defibrillator, atrial ventricular (AV)-block II and III - Systolic blood pressure below 110 or above 160 mmHg at first screening visit - Diastolic blood pressure above 100 mmHg at first screening visit - Heart rate below 50 or above 100 beats / min (taken from ECG measurement) at first screening visit - Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m*2 at first screening visit
Gender	All
Age	30 Years to 80 Years
Accepts Healthy Volunteers	No
Contacts	Not Available
Listed Location Countries	Germany

Administrative Information

NCT Number:	NCT03255512
Other Study ID Numbers	18582 2016-005178-36
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	,
Study Sponsor	Bayer
Collaborators	Merck Sharp & Dohme Corp.
Investigators	Study Director Bayer Study Director Bayer