The purpose of this study is to investigate how quickly and to what extent evobrutinib is absorbed, distributed, metabolized (broken down) and eliminated from the body (this is called pharmacokinetics). Part of the evobrutinib will be labelled with…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the rates and routes of excretion of total radioactivity,
including mass balance of total drug-related radioactivity in urine and feces
To determine the PK of total radioactivity in blood and plasma
To characterize the plasma PK of evobrutinib
Secondary outcome
To assess the safety and tolerability of a single oral 75 mg dose of
[14C]-evobrutinib administered to healthy male participants
Background summary
Evobrutinib is a new compound that may eventually be used for the treatment of
autoimmune diseases (eg. multiple sclerosis (MS), rheumatoid arthritis (RA),
and systemic lupus erythematosus (SLE). Evobrutinib inhibits the response of a
certain type of immsystune cell: B-cells, which play an important role in
diseases such as MS, RA, and SLE.
Study objective
The purpose of this study is to investigate how quickly and to what extent
evobrutinib is absorbed, distributed, metabolized (broken down) and eliminated
from the body (this is called pharmacokinetics). Part of the evobrutinib will
be labelled with 14 Carbon (14C) and is thus radioactive. In this way
evobrutinib can be traced in blood, urine, and feces and it can be measured
when the radioactivity levels in blood, urine and feces reaches the level below
a pre-defined threshold.
Study design
The actual study will consist of one period during which the subject will stay
in the clinical research center for 9 days (8 nights). If the level of
radioactivity in urine and feces is above a pre-defined threshold, this may be
extended up to 6 days (and 6 nights) more during which the subject will stay in
the clinical research center, as is described below.
Day 1 is the day of administration of the study compound. The subjects will
leave the research center on Day 8 up to 14 of the study.
The subject should be aware that when the radioactivity levels are still above
the pre-defined levels on Day 14, he has to return to the clinical research
center on Day 17, 21, 28 and 35 until the radioactivity levels in urine and
feces are below the pre-defined levels.
Intervention
Evobrutinib will be given as an oral solution of 30 milliliters (mL) which will
be administered orally in a syringe after an overnight fast (no eating for at
least 10 hours). After administration of the study compound on Day 1, the
subject will be required to fast for an additional 4 hours. Then he will be
served lunch. Drinking of water is allowed except for from 1 hour before
administration of the study compound until 1 hour after administration of the
study compound.
Study burden and risks
The study compound may cause side effects.
An approximate number of 361 participants (consisting of 183 healthy volunteers
and 178 patients with MS, RA, and SLE) have been exposed to evobrutinib.
Evobrutinib was well tolerated and no relevant adverse events were reported.
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, about 475 milliliters (mL) blood will be taken per volunteer. This
amount does not cause any problems in adults. To compare: a blood donation
involves 500 mL of blood being taken each time.
To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the volunteers arms and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).
Exposure to radiation
This study involves the use of radioactive markers. The amount of radioactivity
will be approximately 3.6 MBq. The average environmental background radiation
burden in The Netherlands is approximately 2.5 mSv per year. The amount of
radiation burden in this study is calculated to be 0,02 mSv. This is below the
limit of 1.0 mSv as determined by the Dutch regulation on radiation protection
and is considered acceptable.
Van Swietenlaan 6
Groningen 9782NZ
NL
Van Swietenlaan 6
Groningen 9782NZ
NL
Listed location countries
Age
Inclusion criteria
1. 18-55 years of age at the time of signing the informed consent.
2. Are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring.
3. Have a body weight within 50.0 and 120.0 kg (inclusive) and Body Mass Index (BMI) within the range 19.0 - 30.0 kg/m2 (inclusive).
4. Male
Exclusion criteria
1. History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.
2. Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to screening.
3. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
4. History of any malignancy.
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 | EUCTR2018-003371-35-NL |
| CCMO | NL67350.056.18 |