The purpose of the study is to investigate how quickly and to what extent BAY 1021189 is absorbed, distributed, metabolized (broken down) and eliminated from the body (this is called pharmacokinetics). The compound to be administered will be labeled…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetics:
plasma drug concentrations, pharmacokinetic parameters.
Secondary outcome
Safety and tolerability:
AEs, vital signs, ECG parameters, laboratory values**, physical examination.
Background summary
BAY 1021189 is a new investigational compound that may eventually be used for
the treatment of heart failure. BAY 1021189 is a stimulator of the enzyme
*soluble guanylate cyclase*, which plays an important role in the regulation of
the cardiovascular system.
BAY 1021189 is not registered as a drug but has been given to humans before.
Study objective
The purpose of the study is to investigate how quickly and to what extent BAY
1021189 is absorbed, distributed, metabolized (broken down) and eliminated from
the body (this is called pharmacokinetics). The compound to be administered
will be labeled with 14-Carbon (14C) and is thus radioactive (also called
radiolabeled). This enables the investigator to trace the compound in blood,
urine and feces. The safety and tolerability of the compound will also be
evaluated.
Study design
The actual study will consist of 1 period during which you will stay in the
clinical research center in Zuidlaren for a minimum of 12 days (11 nights) and
a maximum of 16 days (15 nights), possibly followed by a maximum of 2
additional short visits.
During the study the volunteer will receive the study medication after an
overnight fast (at least 10 hours) as an oral solution. After this the
volunteer is also required to drink an additional amount of 240 milliliters
water. Fasting will continue until 4 hours after administration of study
medication. During fasting and after intake of the study medication, the
volunteer is allowed to drink water ad libitum with the exception of 2 hours
prior to until 1 hour after administration of the study medication.
Intervention
On day 1, a single dose of 5 mg radio-labeled study medication in the form of
an oral solution of 10 milliliters.
Study burden and risks
Blood draw, indwelling canula:
During this study blood will be drawn. In one period 1 time an indwelling
canula will be used and a number of blood draws
will be drawn by direct puncture of the vein. The insertion of the canula may
be associated with pain, minor bleeding,
bruising, possible infection.
As BAY 1021189 is under development there may be side effects, including
allergies, that have not been reported before. Therefore you must notify us of
any new symptoms that you might have, even if you do not think it is related to
the study medication.
BAY 1021189 is under development to treat heart failure. The dose determined
for use in this study has been selected under the premise to avoid serious side
effects.
Approximately 158 healthy male volunteers have received BAY 1021189 in
different studies. In the studies conducted so far the dose range between 0.5
and 10 mg of BAY 1021189 was safe and well tolerated by healthy male
volunteers. The most commonly reported side effects so far were diarrhea,
nausea, and abdominal discomfort. In addition, headache, postural dizziness,
spontaneous penile erection, orthostatic hypotension, ocular hyperemia (red
eyes), and nasal congestion were reported.
At the highest dose tested to date in the first-in-human study (15 mg), 3
volunteers developed orthostatic reactions, i.e., the development of symptoms
upon upright standing after lying down. The symptoms reported included
orthostatic hypotension and fainting. All of these abnormalities recovered
within several days. Because of the development of orthostatic reactions, the
15 mg dose will not be further evaluated. The dose planned to be administered
in this study is 5 mg BAY 1021189.
In this study radiolabeled BAY 1021189 will be used. The amount of
radioactivity in this dose will be 3.7 MBq (MBq = megaBecquerel, this is a unit
to express the amount of radioactivity in the study medication). The average
environmental background radiation burden in The Netherlands is approximately 2
mSv per year (mSv = milliSievert, this is the unit which indicates the burden
on the human body; thus the effect on the human body of the amount of
radioactivity administered). The additional radiation burden in this study due
to the administration of 3.7 MBq 14C-labeled BAY 1021189 is calculated to be
0.96 mSv. This is approximately 48% of the average annual radiation burden.
Aprather Weg 18
Wuppertal 42113
DE
Aprather Weg 18
Wuppertal 42113
DE
Listed location countries
Age
Inclusion criteria
healthy male subjects
45-65 yrs, inclusive
BMI: 18.0-30.0 kg/m2, inclusive
Exclusion criteria
Suffering from hepatitis B, hepatitis C, cancer or HIV/AIDS. In case of participation in another drug study within 60 days before the start of this study or being a blood donor within 60 days from the start of the study. In case of donating more than 1.5 liters of blood in the 10 months prior the start of this study.
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 | EUCTR2013-005115-27-NL |
| CCMO | NL48530.056.14 |