Multiple Dose Study in Heart Failure of BAY 1067197

Heart rate was measured by monitor measurements after 30 minutes resting in a supine position. The relevant changes in heart rate were recorded and analysed.

Blood pressure was measured by monitor measurements after 30 minutes resting in a supine position. The relevant changes in blood pressure were recorded and analysed.

A complete standard 12-lead ECG was recorded and evaluated parameters such as heart rate, PR/PQinterval, QRSD interval, QT interval (uncorrected). Clinically relevant findings in ECG such as a second degree AV-block Mobitz type I (Wenkebach), Mobitz type II - or any third-degree AV block were recorded and reported. A 24-hour Holter ECG was recorded with a standard Holter ECG recorder for the purpose of detecting AV blocks, no higher degree AV blocks > 1 or clinically relevant effect on HR were observed during Holter monitoring periods.

The change in LVEF between the post and the pre-treatment measurements were analyzed using Bayesian statistics to quantify the difference between BAY1067197 treatment and placebo measured by CMR. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart.

Maximum observed BAY84-3174 concentration in plasma, directly taken from analytical data. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

Maximum observed drug concentration, directly taken from analytical data, divided by dose. Geometric mean and %CV were reported.

AUCtau is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after the first dose and dosing interval was 24 h for both arms. Geometric mean and %CV were reported.

AUCtau/D is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval divided by dose after the first dose and dosing interval was 24 h for both arms. Geometric mean and %CV were reported.

Cmax,md is defined as maximum observed drug concentration in plasma after multiple-dose administrations during a dosing interval directly taken from analytical data.Geometric mean and %CV were reported.

Maximum observed drug concentration, directly taken from analytical data divided by dose after multiple doses. Geometric mean and %CV were reported.

AUCtau,md is defined as area under the plasma concentration time profile from time zero during the dosing interval after multiple-dose administrations and dosing interval was 24 h for both arms.

Geometric mean and %CV were reported.

AUCtau,md/D is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after multiple dose of administrations divided by dose and dosing interval was 24 h for both arms. Geometric mean and %CV were reported.

Wall motion score index will cover the changes in wall motion score from baseline also.

Septal mitral annulus (e' septal), Lateral mitral annulus (e' lateral), E/e' average (average of e' lateral and e' septal), E/e' Lateral ratio, E/e' Septal ratio, Peak early doppler transmitral flow velocity (E), Peak atrial doppler transmitral flow velocity (A), E/A Ratio, Deceleration time (DT), Global longitudinal strain, Cardiac output, Stroke volume, Stroke volume index, Peak systolic tissue Doppler Velocity (Smax), Left ventricular end-systolic volume (LVESV), Left ventricular enddiastolic volume (LVEDV), Left atrial volume index (LAVI), Peak pulmonary systolic pressure (PAPsys).

N-terminal prohormone of brain natriuretic peptide (NT-proBNP), renin, mid-region pro-atrial natriuretic peptide (MR-proANP) are biomarkers which show effect on neurohormones.

Time to reach maximum drug concentration in the measured matrix, directly taken from analytical data

AUCtau,md,norm is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval after multiple dosing divided by dose per body weight. The dosing interval was 24 h for both arms. Geometric mean and %CV were reported.

Cmax,md,norm defined as maximum observed drug concentration in plasma after the first dose followed by multiple-dose administrations during a dosing interval divided by dose per body weight. Geometric mean and %CV were reported.

tmax,md defines as time to reach maximum drug concentration in the measured matrix after multiple dose administrations directly taken from analytical data.

t1/2,md is defiend as time to reach maximum observed drug concentration in plasma after the first dose followed by multiple-dose administrations. Geometric mean and %CV were reported.

Cmax,norm is defined as maximum observed drug concentration in plasma after the first dose divided by dose per body weight. Geometric mean and %CV were reported.

AUCtau,norm is defined as area under the plasma concentration time profile from time zero to the end of the dosing interval divided by dose per body weight after the first dose. Dosing interval was 24 h for both arms. Geometric mean and %CV were reported.