The objective of this study is to determine the mass balance and routes of excretion of total radioactivity after a single oral 25 mg dose of [14C]BAY 2433334 given as solution. For further clinical development, human mass balance data are required…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
%AE,ur and %AE,fec (and amount in vomit as a percent of the dose, if
applicable) of BAY 2433334 and its metabolites based on radioactivity excreted
in urine and feces as a percent of the dose to assess mass balance of total
radioactivity
- AUC*, Cmax of total radioactivity in plasma and whole blood
- AUC*, Cmax of BAY 2433334 and BAY 2826102 (and metabolites, if applicable) in
plasma
Secondary outcome
Frequency of participants with treatment emergent adverse events
Background summary
BAY 2433334 is a compound that may potentially be used for the treatment or
prevention of blood clots in the heart, in blood vessels or in the brain as it
can happen after heart attacks, with an irregular heart rhythm or due 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 in the brain it is
called a stroke. All these conditions may ultimately result in death or
permanent disability. BAY 2433334 aims to prevent the formation of the blood
clot (anticoagulation). It works by blocking a *blood clotting* protein (FXIa)
from performing its function.
Study objective
The objective of this study is to determine the mass balance and routes of
excretion of total radioactivity after a single oral 25 mg dose of [14C]BAY
2433334 given as solution. For further clinical development, human mass balance
data are required to elucidate the absorption, distribution,
metabolism, and excretion (ADME) of BAY 2433334.
To quantify total radioactivity in plasma and whole blood.
To quantify BAY 2433334 and BAY 2826102 (M-10 metabolite) concentrations in
plasma.
Evaluate the safety and tolerability of 25 mg BAY 2433334 administered as an
oral solution in healthy male participant.
Study design
The study will consist of 1 period during which the subjects will stay in the
research center for 16 days (15 nights). Day 1 is the day of administration of
the study compound. The subjects are expected at the research center at 11:00
AM in the morning prior to the day of administration of the study compound.
They will leave the research center on Day 15 of the study, or earlier from Day
11 onwards. They will also have to consider 4 additional 24-hour visits for the
collection of urine and feces and to take blood samples. The subject is asked
to collect a feces sample from within 48 hours prior to entry in the clinic.
Intervention
BAY 2433334 will be given as an oral solution of 6.25 milliliters (mL).
Immediately after administration of the study compound the participant will
receive a glass with 240 mL of water, which they will have to drink completely.
All volunteers will receive the same treatment.
The participant will receive 25 mg BAY 2433334 containing 3.7 Mega Becquerel
(MBq) of radioactivity.
Study burden and risks
BAY 2433334 has been administered to in total 172 healthy men before in 4
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. Side effects that were reported include:
• Nausea
• Headcache
• 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*
In previous clinical trials, single doses of 5 mg up to 150 mg have been
administered and were considered safe and well tolerated in healthy male
volunteers. Therefore, the dose that will be used in this study (25 mg
14C-labeled BAY 2433334) is 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 pancreas, liver and
thyroid. 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 function of pancreas, liver, and
thyroid was 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 working mechanism as BAY 2433334 is that they
can result in bleeding. So far, bleedings have not been reported in previous
studies of BAY 2433334 in humans.
An allergic reaction is always possible with a drug that a volunteer has 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.
The study compound may also have side effects that are still unknown.
Drawing blood and/or insertion of the indwelling cannula (tube in an arm vein)
may be painful or cause some bruising. On the day of administration of the
study compound, blood will be sampled very frequently to determine the course
of the concentration of BAY 2433334 in the blood over time.
To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on your arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).
Kaiser-Wilhelm-Allee 1
Leverkusen 51368
DE
Kaiser-Wilhelm-Allee 1
Leverkusen 51368
DE
Listed location countries
Age
Inclusion criteria
Healthy white male
Between 18 and 55 years of age.
BMI is between 18 and 29.9 kilograms/meter2
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 | EUCTR2019-002766-13-NL |
| CCMO | NL72254.056.19 |