The purpose of the study is to investigate how quickly and to what extent BAY 1834845 is absorbed and eliminated from the body (this is called pharmacokinetics). In both study parts it will also be investigated to what extent BAY 1834845 is…
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main objectives of this study are:
To investigate the pharmacokinetics of BAY 1834845 in the absence and presence
of food to determine absolute bioavailability and pharmacokinetics of BAY
1834845 using a simultaneous oral and intravenous [13C6] labeled micro tracer
dose for the effect of a single oral dose of BAY 1834845 On the
pharmacokinetics of a single oral dose of methotrexate administered.
Secondary outcome
The secondary objectives are to investigate safety and tolerability of BAY
1834845 with and without methotrexate.
Background summary
BAY 1834845 is a new investigational compound that may eventually be used for
the treatment of immune-mediated diseases such as rheumatoid arthritis (RA). In
these diseases the immune system reacts in an abnormal way to normal body
tissue. It is expected that BAY 1834845 will reduce inflammatory reactions
because BAY 1834845 interacts with one of the enzymes involved in immune
responses (interleukin-1 receptor-associated kinase 4 or IRAK4) BAY 1834845 is
in development and is not registered as a drug but has been given to humans
before.
If you participate in Part B of this study, the volunteer will also receive
methotrexate. Methotrexate is a drug often used in the treatment of RA.
Study objective
The purpose of the study is to investigate how quickly and to what extent BAY
1834845 is absorbed and eliminated from the body (this is called
pharmacokinetics). In both study parts it will also be investigated to what
extent BAY 1834845 is tolerated.
Part A: the effect of food on the absorption of BAY 1834845 will be
investigated.
Part B: the effect of BAY 1834845 on the absorption and elimination of
methotrexate will be investigated.
Study design
Part A:
The actual study will consist of 3 periods during which the volunteer will stay
in the clinical research center in Groningen (location UMCG) for 9 days (8
nights). The time interval between the administrations of the study compound is
at least 14 days.
During the study the volunteer will receive BAY 1834845 as a single tablet with
240 milliliters of water.
All volunteers will receive the study compound twice with a breakfast and once
without a breakfast, however the order in which this will occur will be
determined by chance. In one period the volunteer will receive BAY 1834845
after a standardized high fat breakfast which will have to be finished within
20 minutes. The entire breakfast must be consumed. In the second period the
volunteer will receive BAY 1834845 after an overnight fast (at least 10 hours
no eating and drinking). In the third period, the volunteer will receive a
standardized medium fat breakfast which will have to be finished within 20
minutes. The entire breakfast must be consumed.
For all periods it is applicable that after the fasted administration, fasting
will continue until 4 hours after administration of the study compound. Then
the volunteer will receive a lunch. During fasting the volunteer are allowed to
drink water with the exception of 1 hour prior to administration of the study
compound.
One of the investigators will inspect the hands and mouth after the study
compound intake.
After administration of the oral study compound without a breakfast, an i.v.
administration of 0.1 mg 13C6 BAY 1834845, lasting 15 minutes will be given.
This administration will start approximately 3 hours after the intake of the
tablet.
Part B:
The actual study will consist of 2 periods during which the volunteer will stay
in the clinical research center in Groningen (location UMCG) for 4 days (3
nights) followed by 1 day (Day 5; Day 1 is the day of administration of the
study compound) during which the volunteer will visit the clinical research
center in Groningen for a short visit. The time interval between the different
periods is at least 7 days.
During the study the volunteer will receive 3 tablets methotrexate with or
without 2 - 4 tablets BAY 1834845 after an overnight fast (at least 10 hours no
eating and drinking) or after a standardized breakfast, with 240 milliliters of
water. You will be informed about the time of BAY 1834845 administration and
whether the volunteer will get a breakfast and which type of breakfast when the
volunteer enter the clinical research center for the first period. If the
volunteer receive BAY 1834845 twice, the first dose will be given in the
evening of the day the volunteer arrive in the clinical research center.
For both periods it is applicable that fasting on Day 1 will continue until 4
hours after administration of the study compound. Then the volunteer will
receive a lunch. During fasting the volunteer is allowed to drink water with
the exception of 1 hour prior administration of the study compound.
One of the investigators will inspect the hands and mouth after the study
compound intake.
Intervention
Part A:
During the study you will receive BAY 1834845 as an oral tablet with 240 mL
water.
The study will consist of 3 periods during each of which the volunteer will
receive one dose of BAY 1834845. BAY 1834845 will be given as an oral tablet
containing 120 mg of the study compound. You will receive the study compound
once without food (fasted), once with a breakfast with high fat content and
once with a normal breakfast. During the period in which the volunteer receive
the study compound fasted, the volunteer will also receive 0.1 mg carbon-13
(13C) enriched BAY 1834845 (see below) as an intravenous (i.v.) infusion of 15
minutes.
The i.v. infusion will contain the study compound *enriched* with 6 13C atoms
at specific places in the study compound. 13C is a natural, stable (not
radio-active) carbon isotope, a variant of carbon which contains a different
number of neutrons compared to normal carbon (12C). In this case 1 extra
neutron is present in the atom core and as a result the isotope weighs more and
can be detected separately.
Part B:
The study will consist of 2 periods during which the volunteer will receive 7.5
mg methotrexate with or without BAY 1834845 once. Methotrexate and BAY 1834845
will be given as tablets. Whether the volunteer will receive methotrexate with
or without BAY 1834845 in a period will be determined by chance. The amount of
BAY 1834845 will be determined later - based on the results of Part A and of
another ongoing study with BAY 1834845 - but will be between 240 and 480 mg (2
times 120-240 mg with 12 hours in between, or once 240-480mg). You will be
informed about time of dosing and the actual amount before the administration
of the study compound.
Please refer to the table below to see the planned treatments:
Treatment Sequence Period 1 Number of tablets Period 2 Number of
tablets
1 7.5 mg Methotrexate 3 7.5 mg Methotrexate 3
240-480 mg BAY 1834845 2-4
2 7.5 mg Methotrexate 3 7.5 mg Methotrexate 3
240-480 mg BAY 1834845 2-4
Study burden and risks
All potential drugs cause side effects; The extent to which this happens
differs. There is no substance similar to BAY 1834845 on the market. Research
has already been done or is currently being done with a similar means. However,
no data is yet available. In a study currently being conducted with BAY
1834845, the drug was well tolerated in single doses up to 480 mg. The
following side effects are most commonly observed in this study: an increase in
blood of C-reactive protein (a protein associated with inflammatory reactions
in the body), headache and colds. Other important side effects that have been
observed include coughing, increased amount of bilirubin in the blood, nausea,
dizziness, abdominal flu and nasal cold.
The results of the pre-clinical study with BAY 1834845 indicate that serious
side effects are unlikely. When investigating the impact on the immune system,
no relevant differences were found. There are no indications that BAY 1834845
may alter the genetic material in cells (genotoxicity) and no evidence of
effects on the skin when exposed to sunlight (phototoxicity).
BAY 1834845 interacts with one of the enzymes involved in immune responses
(IRAK4) and is expected to decrease the immune reaction. In this study the
protein IRAK4 will be inhibited only briefly by a single administration of the
study compound. Therefore it is not expected that you will be at an increased
risk of serious infections; however, an increased susceptibility to infections
cannot be excluded entirely. In this study, inflammatory parameters will be
tested in addition to the standard laboratory parameters in order to identify
any unexpected changes at an early stage.
There is a theoretical risk of hypersensitivity / allergic reactions.
Methotrexate is a drug that has been on the market in low doses as a treatment
for rheumatoid arthritis and other immune-mediated diseases for over 25 years.
The most common adverse effects of low dose methotrexate are bone marrow
suppression, resulting in a decreased production of blood cells, leucopenia,
and mucosal damage which manifest as ulcerative stomatitis, nausea and other
gastrointestinal disorders. Other frequently occurring adverse reactions
include e.g. herpes zoster, malaise, abnormal fatigue, chills and fever,
dizziness and reduced immunity to infections. The adverse effects are more
common during long-term use. In studies with healthy volunteers the following
adverse effects were reported: nausea, vomiting, dizziness, headache, abdominal
discomfort, and loose stools.
Müllerstrasse 178
Berlin 13353
DE
Müllerstrasse 178
Berlin 13353
DE
Listed location countries
Age
Inclusion criteria
- healthy male subjects
- 18 - 50 years, 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 3 months before the start of this study. In case of donating more than 0.5 liters of blood in the 4 week prior the start of this study.
Design
Recruitment
Medical products/devices used
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 | EUCTR2016-004393-18-NL |
CCMO | NL62710.056.17 |