Single dose escalation study to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BAY 2413555 after oral dosing in healthy male participants in a randomized, single-blind, placebo-controlled, group-comparison design

BAY 2413555 is a new compound that may eventually be used for the treatment of
heart failure. Heart failure is a serious disease and after diagnosis 45% to
60% of heart failure patients will die within 5 years after diagnosis. BAY
2413555 can indirectly modulate the so-called muscarinic M2 acetylcholine
receptor. The muscarinic M2 acetylcholine receptor is located on heart muscle
cells and when activated it will decrease the heart rate and may improve the
heart function.

The purpose of this study is to investigate how safe the new compound BAY
2413555 is and how well it is tolerated when it is administered as a single
oral dose to healthy volunteers. BAY 2413555 has not been administered to
humans before. It has been previously tested in the laboratory and on animals.
BAY 2413555 will be tested at various dose levels.

It will also be investigated how quickly and to what extent BAY 2413555 is
absorbed and eliminated from the body. In addition, the effect of BAY 2413555
on indicators related to the heart function will be investigated.

The subjects will stay in the research center for maximal 12 days (11 nights).

Day 1 is the day of administration of the study compound.

Depending on the group in which the volunteer will participate, the study
compound will be given once either as a tablet or as an oral solution with a
maximum of 20 milliliter (mL), depending on the dose. Thereafter the volunteer
is also required to drink an additional amount of 240 mL of water.

Day 1 is the day of study compound administration. On the day before (Day -1)
and on the day of study compound administration (Day 1) the subjects will need
to lie down resting for most of the time (up to noon on Day 2). This is
important to collect stable values for blood pressure and heart rate. This
means that overall, the subjects have to stay in bed starting from Day -1 up to
noon on Day 2 (3 days in total), and have to remain in supine position for most
of the time. If there are no assessments during the bed rest phase, subjects
may take a semi-supine position. On Day 1 sybjects have to completely stay in
bed for the first 6 hours after dosing and the same time on Day -1. Subjects
will stand up for your first meal (lunch) and afterwards they may rise during
this bed rest phase after asking the study personnel, for example for using the
bathroom. The subjects will then be accompanied by personnel.

Per group, 8 volunteers will receive BAY 2413555 and 2 volunteers will receive
placebo.

An ambulatory follow-up visit, performed 11 to 14 days after administration of
the study drug. Based on the results of prior dose groups, an additional
follow-up visit may be performed between 15 and 20 days after administration of
the study drug.

Possible discomforts due to procedures
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising. Inflammation of the vein, nerve injury, and vasovagal
reactions (faint due to e.g. blood draw) may occur as well.

In total, about 500 milliliters (mL) of blood will be taken within
approximately 6 weeks. This amount does not cause any problems in adults.

To make a heart tracing (ECG) and monitor the heart rate (telemetry and Holter
monitoring), electrodes will be pasted at specific locations on the arms,
chest, abdomen and legs. Prolonged use of these electrodes can cause skin
irritation.

In the standing blood pressure testing subjects might feel dizziness, nausea or
might lost consciousness which might occur already before dosing.

Due to the long period that subjects have to remain in bed in a supine or
semi-supine position, the many assessments that will be done on certain days
and the connection to the telemetry and Holter devices for most of the time,
subjects should be aware that this study can be considered an intensive study
and they might feel tiredness, headache or have other discomfort. Such as a
feeling of hunger due to long-term fasting conditions that have to be strictly
followed during the course of the study.

A sample for the coronavirus test will be taken from the back of the nose and
throat using 2 swabs. Taking the sample only takes a few seconds but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
your throat may cause the volunteer to gag. When the sample is taken from the
back of the nose, the volunteer may experience a stinging sensation and the
eyes may become watery.

If the test is positive during the study and you received BAY2413555, the
volunteer will be monitored at the research center (in quarantine), as long as
was originally planned for him. This is a measure of safety as the study
compound might still be in the body.