Heart Failure

Inclusion Criteria

- Stable systolic heart failure (heart failure with reduced ejection fraction, heart failure with reduced ejection fraction [HFrEF]; New York Heart Association [NYHA] I-III) in sinus rhythm with a documented ejection fraction (EF) ≤45% within the last 3 months
 - Stable standard heart failure (HF) therapy including intermediate to high dose β-blocker with either ≥ 95 mg metoprolol succinate (controlled release tablet), ≥ 5mg Bisoprolol (immediate release [IR] -tablet) or ≥5mg Nebivolol (IR tablet) for at least 4 weeks. Additional intake of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers and optional aldosterone-receptor antagonists, diuretics or digitalis is allowed
 - Men or confirmed postmenopausal women (defined as being amenorrheic for longer than 2 years with an appropriate clinical profile, e.g. age appropriate and a history of vasomotor symptoms) or women without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy (documented by medical report verification). Men enrolled in this study must agree to use adequate barrier birth control measures during the treatment period of the study and for 12 weeks after receiving the investigational medicinal product (IMP)
 - Male patients must agree not to act as sperm donor for 12 weeks after dosing
 - Ethnicity: White
 - Body mass index (BMI): above/equal 18.0 and below/equal 29.9 kg/m²    
 - Age: 18 to 75 years (inclusive) at the first screening visit

Exclusion Criteria

- Biventricular pacing/active cardiac resynchronization therapy (CRT) device
 - Dependency on pacemaker or implantable cardioverter-defibrillator (ICD) device with pacemaker dependency (a paced ventricular rhythm > 5% of heart activity)
 - A history of relevant diseases of vital organs other than the heart, of the central nervous system or other organs
 - Known hypersensitivity to the study preparations (active substances or excipients of the preparations) or to any other β-blocker
 - Current or history of AV-Block > I°
 - Unstable condition, indicated by requirement of IV drug (diuretic, inotrope, etc.) or NYHA IV
 - Acute Coronary Syndrome (defined as unstable angina [UA], non-ST elevation myocardial infarction [NSTEMI], ST elevation myocardial infarction [STEMI]) within 3 months prior to first study drug administration
 - History of asthma or chronic obstructive pulmonary disease (COPD) ≥ global initiative for chronic obstructive lung disease (GOLD) II and/or allergic asthma     
 - Women of childbearing potential, pregnancy or breastfeeding