Single dose escalation study in a single-center, randomized, single-blind, placebo-controlled, group-comparison design to investigate pharmacokinetics, safety and tolerability of BAY 2586116 after intravenous administration in healthy male participants.

BAY 2586116 is a compound that may potentially be used for the treatment of
obstructive sleep apnea (OSA). OSA belongs to the most common chronic
(long-lasting) diseases of the respiratory system. In patients with OSA, soft
tissue in the back of the throat relaxes during sleep. Because of this, the
airways are narrowed and the flow of oxygen to the lungs is hindered. Symptoms
of this disease are daytime sleepiness, snoring, headache, and disrupted sleep,
which all negatively affect the quality of life. BAY 2586116 could potentially
prevent the relaxation of the soft tissue in the back of the throat. BAY
2586116 has already been tested in humans before in the form of a nasal spray,
which is the intended use. In the current study, an intravenous infusion will
be used to test doses that are higher than would be used in the actual
treatment of a patient. These doses cannot be reached with the nose spray in
healthy volunteers. It is important to know how the body reacts to higher
doses, as future patients might get higher levels of the study compound in
their blood due to organ impairment, interactions with other drugs they might
take, or misuse of the dosage form.

The purpose of this study is to investigate how quickly and to what extent the
study compound BAY 2586116 is absorbed and eliminated from the body. It will
also be investigated how safe the new compound BAY 2586116 is and how well it
is tolerated when it is administered to healthy male volunteers. Furthermore,
we will investigate if the study compound has an effect on heart activity. This
is why the heart activity will be monitored closely by regularly recording the
electrical activity of the heart (electrocardiogram, ECG). Furthermore, the
effect of the genetic information on the volunteer body*s response to BAY
2586116 might be investigated.

BAY 2586116 is an investigational compound. It is not approved for sale in any
country as it is still under development. Therefore, BAY 2586116 can only be
used in studies like this one. BAY 2586116 has already been administered to 64
humans before over 2 previous clinical trials. It has also been extensively
tested in the laboratory and on animals.

The study will be conducted in up to 35 healthy male volunteers.

The volunteers will be divided into groups called dosing steps. One can
participate in one of these groups.

The effects of BAY 2586116 are compared with the effects of a placebo.

The actual research consists of 1 period during which the volunteers will stay
in the research center for 5 days (4 nights).

Day 1 is the day the study drug is administered. The volunteers are expected at
11:00 in the morning 2 days prior to the day of study drug administration in
the study center (i.e. on Day -2). The entry time can be adjusted. The research
center is left on Day 3 of the examination.

Prior to receiving the study drug on the day of dosing (Day 1), one should fast
for at least 10 hours overnight. BAY 2586116 or placebo is then given as an
intravenous infusion. The infusion lasts 30 minutes.

The volunteer will not be allowed to leave the bed during the first 4 hours
after administration of the study compound. This is a safety precaution, as the
study compound may have side effects that are still unknown as BAY 2586116 is
for the first time being administered to humans directly into the vein.
Therefore, the volunteer will be closely monitored directly after
administration, and he can only leave the bed when accompanied by study
personnel.

Whether one gets BAY 2586116 or placebo is determined by drawing lots. Per
dosing step, 5 volunteers receive BAY 2586116 and 2 volunteers receive placebo.

Prior to receiving the study drug on the day of dosing (Day 1), one should fast
for at least 10 hours overnight. BAY 2586116 or placebo is then given as an
intravenous infusion. The infusion lasts 30 minutes.

The volunteer will not be allowed to leave the bed during the first 4 hours
after administration of the study compound. This is a safety precaution, as the
study compound may have side effects that are still unknown as BAY 2586116 is
for the first time being administered to humans directly into the vein.
Therefore, the volunteer will be closely monitored directly after
administration, and he can only leave the bed when accompanied by study
personnel.

Whether one gets BAY 2586116 or placebo is determined by lot. Per dosing step,
5 volunteers receive BAY 2586116 and 2 volunteers receive placebo

BAY 2586116 has been administered to 64 humans before in 2 previous clinical
trials. In these studies, the study compound was administered as a nose spray.
The current study is the first study where the study compound will be
administered via an infusion. Knowledge about possible side effects in humans
is therefore still limited.

In one clinical trial, a single dose of BAY 2586116 was administered as a nose
spray with doses from 12 µg to 160 µg. BAY 2586116 was considered safe and well
tolerated.

In the other study, once daily doses of BAY 2586116 as a nose spray were
administered at doses of 50 µg, 80 µg, and 160 µg over 5 days. In this study,
no side effects were reported that were judged as being possibly related to the
study compound.

On the day of administration of the study compound, blood is drawn using an
indwelling cannula from a blood vessel in the forearm to determine the course
of the concentration of BAY 2586116 in the blood over time. This might
sometimes cause mild pain, inflammation, swelling, hardening of the vein, blood
clotting and bleeding into surrounding (bruising) at the insertion site. In
rare cases, there may be inflammation and damage to blood vessels and/or damage
to neighboring nerves. In sensitive individuals, blood draws may sometimes
cause pallor, nausea, sweating, slow pulse, or drop in blood pressure with
dizziness or fainting. The use of adhesive bandages to cover blood draw sites
may cause mild, temporary redness and itching of the skin.

For the intravenous administration of the study compound, an extra indwelling
cannula will be inserted on Day 1 in addition to the indwelling cannula used
for blood sampling. Thus, the volunteer will have a cannula inserted in both
arms during the 30 minute infusion of the study compound.

In total, we will take about 130 milliliters of blood. Based on the discretion
of the responsible doctor, extra samples might be taken to guarantee the safety
of the participants.

To make a heart tracing, electrodes will be pasted on their arms, chest and
legs. To monitor the heart rate with telemetry, electrodes will be pasted on
the chest and abdomen. Prolonged use of these electrodes can cause reddening
and/or itching of the skin.

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