The study consists of a Pilot Phase (to assess safety and the local tolerability of highest AOP LDLA202 dose versus placebo) and a Main Treatment Phase (to compare PK, PD and safety and tolerability of AOP LDLA202, ONO LDL50 and esmolol bolus administrations by measurement of blood concentrations of landiolol, esmolol and their metabolites, and by monitoring ECG, blood pressure and adverse events).

A single centre prospective, randomized, double blind study consisting of a local safety Pilot Phase and a triple-cross-over Main Study Phase.

In the pilot phase, 3 subjects will be administered a bolus with AOP LDLA202 vs. placebo (0.9% saline) simultaneously (same vein on the other body side). Following treatment of the first subject per cohort and assuming no safety concerns arise, second and third subjects will be treated in safety intervals of at least 3 hours between doses in individual subjects. On Day 3 after dosing a safety follow-up assessment will be done and all adverse events will be reported to the sponsor's medical monitor. Assuming no safety concerns arise, the sponsor's medical monitor will give green light for conduct of the Main Treatment Phase in writing.

In the main phase, 12 subjects will be treated with AOP LDLA202, ONO LDL50 and esmolol. Three doses per subject and day (=treatment period), all administered via big superficial veins, are planned with at least 1 hour observation period after each bolus injection. Each subject, if confirmed eligible, will complete three treatment periods in total in the main phase of the study.

ECG, blood pressure, local tolerability and adverse events will be monitored.

Inclusion Criteria:

• Male and female human subjects, age 18-45 years, Caucasians
• Body weight of at least 50 kg, maximum of 90 kg. Body-mass index 18.5 to 30.0 kg/m2.
• Subjects without clinically relevant abnormalities as determined by baseline medical history, physical examination, blood pressure, heart rate and ear temperature at screening.
• Subjects without clinically relevant abnormalities as determined by blood count, coagulation tests, biochemistry, infectious disease screening, urinalysis, ECG, and 2D Echo at screening.
• Subject is willing and able to undergo procedures required by this protocol and gave written informed consent.
• Agreeing to not using any prescription and over the counter medications
• No history or presence of alcoholism or drug abuse

Exclusion Criteria:

• Subjects with history or presence of clinically relevant cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic, hematological, gastrointestinal, endocrine, immunological, psychiatric or skin diseases.
• Subjects with bradycardia (heart rate below 50 bpm), tachycardia (heart rate above 100 bpm), hypotension (systolic blood pressure below 100 mmHg, and/or diastolic blood pressure below 70 mm Hg) at screening, history of clinically relevant arrhythmias.
• Subjects with clinically relevant cardiac supraventricular or ventricular arrhythmias.
• Subjects with atrioventricular block of grade II and III, sick sinus syndrome, sinoatrial block or congestive heart failure.
• Participation in a clinical drug study or bioequivalence study 60 days prior to present study.
• History of malignancy or other serious diseases.
• Any contraindication to blood sampling.
• History of i.v. drug abuse.
• Subjects with positive HIV tests, HBsAg or Hepatitis C tests or other acute, subacute or chronic infectious disease.
• Known history of hypersensitivity to any IMP.
• Refusal to abstain from smoking or consumption of tobacco products 48 hours before drug administration and during the study period.
• Refusal to abstain from alcohol, caffeine, or other xanthines, or grapefruit containing food or drinks for 72 hours before drug administration and during the study period.
• Refusal to abstain from strenuous activities for 7 days before screening and end-of-study examinations, before and during each study period.
• Subjects with anomalies of the venous and arterial vessels of the forearms or systemic vascular diseases.
• Pregnancy and/or breast-feeding.