Single dose escalation study in a single center, randomized, single blind, placebo controlled, group comparison design to investigate pharmacokinetics, safety and tolerability of BAY 2253651 after intravenous administration in healthy male subjects.

BAY 2253651 is a new compound that may eventually be used for the treatment of
obstructive sleep apnea. Obstructive sleep apnea is a common respiratory
disorder that involves repetitive occlusion of the airway of the pharynx while
sleeping. This leads to oxygen deficiency and sleep disruption. Other symptoms
include daytime sleepiness, snoring and headache.

BAY 2253651 is a compound which promises to increase the activity of the
genioglossus muscle (the major tongue muscle). Normally, inspiration results in
a negative pressure in the pharynx. This negative pressure induces a
reflex-driven activation of the genioglossus muscle. In obstructive sleep
apnea, this reflex is diminished. BAY 2253651 can sensitize the upper airway
receptors resulting in an increased reflex activity of the genioglossus muscle,
thereby stimulating opening of the airway.

There is currently no drug treatment for obstructive sleep apnea. A non
invasive and easy-to-use therapy would represent a benefit for many patients
who suffer from this disease. Because BAY 2253651 acts locally, application of
a liquid formulation using a pump spray into the nose is the provided route of
administration. However, for the further clinical development of BAY 2253651,
it is necessary to investigate the pharmacokinetics of BAY 2253651 when
administered intravenously, via a tube in an arm vein. BAY 2253651 has been
administered, via the nose, in humans before.

The main purpose of this study is to investigate how quickly and to what extent
BAY 2253651 is absorbed (taken up), distributed, metabolized (broken down) and
eliminated from the body (this is called pharmacokinetics). Multiple dose steps
of BAY 2253651 will be tested. Furthermore, it will be investigated how safe
BAY 2253651 is and how well BAY 2253651 is tolerated.

The effects of BAY 2253651 will be compared to the effects of a placebo. A
placebo is a medicine without any active ingredient. It is a *fake* medicine.

The study consists per volunteer of 1 period in which the volunteer stays for 5
days (4 nights) in the research center.

A single dose of BAY 2253651 or placebo will be given as an intravenous
infusion (solution of the compound that will be administered directly in a
blood vessel) over 20 minutes. The volunteer will have to remain lying down
during 4 hours after administration of the study compound.

Administration of the study compound will be done after an overnight fast of at
least 10 hours. During fasting you are allowed to drink non-sparkling water,
except from 1 hour before until 1 hour after administration of the study
compound. Following administration, you will fast for another 4 hours. A
standardized lunch, snack and dinner will be provided 4, 8 and 10 hours after
administration of the study compound, respectively. The same schedule of food,
drinks and fasting will be followed on the day before administration of the
study compound (so on 2 consecutive days).

Whether the volunteer will receive BAY 2253651 or placebo will be determined by
chance. Per group, 5 volunteers will receive BAY 2253651 and 2 volunteers will
receive placebo. They will not know if BAY 2253651 or placebo is administered
whereas the responsible doctor will know this; we call this a single-blinded
study.

Group 1: BAY 2253651 or placebo; 5 µg Intravenous solution, once
Group 2 to 5: BAY 2253651 or placebo, once by intravenous solution.
Height of dose depends on the results of the previous groups.

Blood sampling
During this study, small amounts of blood will be drawn from a vein and used
for routine laboratory tests and for pharmacokinetic testing. Drawing blood may
cause pain where the needle is inserted, and there is a small risk of bruising
or infection at the place where the needle is inserted. Very rarely, a blockage
of the vein or a small nerve injury can occur, resulting in numbness and pain.
However, this will resolve with time. Some people experience dizziness, upset
stomach, or fainting when their blood is drawn.

The use of adhesive bandages to cover the blood draw sites may cause mild,
temporary redness and itching of the skin.

On days when several blood samples will be taken, a cannula (small plastic
tube) will be inserted in a vein of the arm using a small needle. This cannula
may remain in place for a longer period of time. There is a small chance of
infection by placing the cannula in the vein, but every medical precaution will
be taken to avoid an infection.

In total, we will take about 120 mL of blood from the volunteer. This amount
does not cause any problems in adults. To compare: a blood donation involves
500 mL of blood being taken each time and is allowed 5 times per year.

Heart tracing (ECG) and Holter
Electrodes (small, plastic patches) will be placed temporarily on different
parts of your body. There is no pain or discomfort during an ECG or Holter
measurement (recording heart rhythm). However, the area of the skin where the
patches will be stuck may need to be shaved, and the patches may cause a skin
reaction such as redness or itching. Taking the patches off may cause localized
irritation to the skin and/or hair loss, similar to having a plaster taken off.