The purpose of this study is to investigate how quickly and to what extent BAY 2433334 is absorbed, broken down, and eliminated from the body (this is called pharmacokinetics). The pharmacokinetics of BAY 2433334 administered as a tablet will be…
ID
Source
Brief title
Condition
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate the absolute bioavailability and pharmacokinetics of BAY 2433334
using a simultaneous oral unlabeled and i.v. [13C7,15N]-labeled microdose.
Secondary outcome
To investigate safety and tolerability of BAY 2433334.
Background summary
BAY 2433334 is a compound that may potentially be used for the prevention of
blood clots in the heart, in blood vessels or in the brain as it can happen
after heart attack or stroke, with an irregular heart rhythm or due to other
reasons. Worldwide, disease of the heart or blood vessels is the leading cause
of death in adults with an estimated 17.7 million deaths in 2015. BAY 2433334
is a blood thinner (an *anti-coagulant*) which can prevent the formation of
blood clots in blood vessels (so-called *thrombo-embolic* disorders). These
blood clots can travel through the bloodstream and block arteries which
prevents blood from delivering oxygen and nutrients to the organs. When that
happens in the heart, it is called a heart attack and when that happens in the
brain it is called a cerebral infarction, also called stroke. All these
conditions may ultimately result in death or permanent disability. BAY 2433334
aims to prevent the formation of blood clots (anticoagulation). It works by
blocking a *blood clotting* protein (FXIa) from performing its function.
Study objective
The purpose of this study is to investigate how quickly and to what extent BAY
2433334 is absorbed, broken down, and eliminated from the body (this is called
pharmacokinetics). The pharmacokinetics of BAY 2433334 administered as a tablet
will be compared to the pharmacokinetics of BAY 2433334 administered as
intravenous (iv; in the vein) infusion.
It will also be investigated how safe BAY 2433334 is and how well it is
tolerated when it is administered to healthy male volunteers. Furthermore, the
effect of your genetic information on your body*s response to BAY 2433334 will
be investigated.
The iv infusion of BAY 2433334 will be a very low dose (microdose) which will
be labeled with carbon-13 (13C7) and nitrogen-15 (15N). Carbon-13 and
nitrogen-15 are isotopes. Isotopes are atoms of the same element with the same
number of protons, but with a different number of neutrons in the atom nucleus.
Carbon-13 and nitrogen-15 both have a neutron more than their normal elements.
As a result, they are heavier and can be measured separately so that the
absolute bioavailability can be determined (pharmacokinetics of BAY 2433334
tablet without isotopes compared to pharmacokinetics of BAY 2433334 iv infusion
with isotopes). The carbon-13 and nitrogen-15 isotopes are not radioactive.
BAY 2433334 is an investigational compound. It is not approved for sale in any
country. That means it can only be used in studies like this one. BAY 2433334
has been administered to healthy volunteers before. It has also previously been
extensively tested in the laboratory and on animals.
The study will be performed in up to 16 healthy male volunteers.
Study design
The actual study will consist of 1 period during which the volunteers will stay
in the research center for 5 days (4 nights).
Day 1 is the day of administration of the study compound. Volunteer is expected
at the research center at 11:00 hrs in the morning one day prior to the day of
administration of the study compound (Day -1). Volunteer will leave the
research center on Day 4 of the study.
Volunteer will be tested for the presence of coronavirus at the visit on Day -5
or -4 and upon admission to the research center on Day -1. Until the test
results are available, volunteer will be separated from other volunteers and
only have very limited contact with study staff. This is to avoid virus spread
from potentially infected volunteers to other volunteers or to the study staff
because, until the results are available, it is not certain whether the
volunteer is infected or not and can thus potentially infect others. The test
results will be available within a few hours. If volunteer test positive for
coronavirus, he cannot participate in the study. It may be decided that more
tests are needed (eg, if volunteer has COVID-19 symptoms).
Intervention
On day 1, the volunteers are administered 25 mg of BAY 2433334 followed 2 hours
later by 50 µg of 13C7.15N-labeled BAY 2433334.
Study burden and risks
BAY 2433334 has been administered to in total 219 healthy men before in 7
previous clinical studies. These studies found no relevant effects of BAY
2433334 on several health parameters, including heart tracings (ECGs), blood
pressure, and heart rate. BAY 2433334 was considered safe and well tolerated.
Side effects that did occur were:
• Nausea
• Headache
• Dizziness
• Dry mouth
• Bitter taste sensation
• Fast or irregular heartbeat
• Tingling or pricking sensation (paresthesia) in hands and fingertips
• Sensation of cold in feet
• Sensation of *lump in the throat*
The side effects disappeared again after a few hours. Only the irregular
heartbeat was observed over a longer period of approximately 1 day.
In previous clinical trials, single doses of 5 mg up to 150 mg of BAY 2433334
and multiple doses of 25 mg up to 100 mg BAY 2433334 were administered and were
considered safe and well tolerated. Therefore, the single oral dose that will
be used in this study (25 mg BAY 2433334) and the intravenous micro dose (50 µg
BAY 2433334) are also expected to be safe and well tolerated.
BAY 2433334 has been studied extensively in the laboratory and in animals.
Studies in animals showed effects of BAY 2433334 on the liver. Therefore,
intensive monitoring is used in the human studies to make sure human volunteers
do not develop similar signs or symptoms. In all the previous studies in
humans, no changes in the liver function were found after administration of BAY
2433334.
The mode of action of BAY 2433334 is to slow down the clotting of blood. A risk
of compounds that have a similar mode of action (blood thinners) is that they
can result in spontaneous bleeding. As the working mechanism of BAY 2433334 is
slightly different than that of other blood thinners, spontaneous bleedings
with BAY 2433334 are less likely. The main risk associated with BAY 2433334 is
assumed to be increased bleeding after trauma or surgery. So far, bleedings
have not been reported in previous studies when BAY 2433334 was administered to
humans.
The study compound may also have side effects that are still unknown. In
addition to unknown side effects, there is a (small) chance that an allergic
reaction will occur. This can be caused by the study compound or the other
ingredients used to make the formulation.
An allergic reaction is always possible with a drug you have not taken before.
Unexpected serious allergic reactions can be life-threatening. Some things that
may happen during an allergic reaction to any type of medication include rash,
breathing difficulty, sudden drop in blood pressure, swelling of
mouth/throat/eyes, fast pulse and/or sweating.
Possible discomforts due to procedures
On the day of administration of the study compound, blood is drawn using an
indwelling venous cannula from a blood vessel in the forearm. 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. On the day of administration of the study compound,
blood will be sampled very frequently (20x ) by using an indwelling cannula to
determine the course of the concentration of BAY 2433334 in the blood over
time. The use of adhesive bandages to cover blood draw sites may cause mild,
temporary redness and itching of the skin.
For the intravenous administration, an extra indwelling cannula will be
inserted on Day 1 in addition to the indwelling cannula used for blood
sampling. Thus, the volunteers will have a cannula inserted in both arms during
the 30-minute infusion of the study compound.
In total, we will take about 170 milliliters (mL) of blood from you.
To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).
A sample for the coronavirus test will be taken from the back of the nose and
throat using a swab. 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
the throat may cause volunteer to gag. When the sample is taken from the back
of the nose, volunteer may experience a stinging sensation and the eyes may
become watery.
Kaiser-Wilhelm-Allee 1
Leverkusen 51368
DE
Kaiser-Wilhelm-Allee 1
Leverkusen 51368
DE
Listed location countries
Age
Inclusion criteria
• healthy white male
• 18 to 45 years old at the time of the screening visit
• BMI is between 18 and 29.9 kilograms/meter2
• not regularly drink more than 17.5 units of alcohol per week. 17.5 units of
alcohol is equal to approximately 12 glasses (285 mL) of beer or lager, 12
glasses (125 mL) of wine, or 17 small shots (25 mL) of spirits.
• do not regularly consume more than 1 L of methylxanthine or
caffeine-containing beverages daily.
• did not donate more than 100 mL of blood or plasma within 4 weeks or 500 mL
blood within 3 months before study compound administration. Blood donation is
not allowed during the entire study, until 3 months after the last visit.
• not participated in any other drug study within 3 months preceding the
administration of the study compound.
• no history of COVID-19 infection, do not test positive in the SARS-CoV-2
test, and no contact with SARS-CoV-2-positive or COVID-19 patients within 4
weeks prior to admission to the research center.
• at screening the state of health must satisfy the study entry requirements.
Exclusion criteria
1. A history of relevant diseases of vital organs, of the central nervous
system or other
organs.
2. Medical disorder, condition or history of such that would impair the
participant*s ability to participate or complete this study in the opinion of
the investigator.
3. Incompletely cured pre-existing diseases for which it can be assumed that
the absorption, distribution, metabolism, elimination and effects of the study
intervention will not be normal.
4. Known hypersensitivity to the study interventions (active substance or
excipients of
the preparation).
5. Known severe allergies e.g. allergies to more than 3 allergens, allergies
affecting the
lower respiratory tract - allergic asthma, allergies requiring therapy with
corticosteroids, urticaria or significant non-allergic drug reactions.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004049-34-NL |
| CCMO | NL74123.056.20 |