The purpose of the study is to investigate how quickly and to what extent cenerimod is absorbed, distributed, metabolized (broken down) and eliminated from the body (this is called pharmacokinetics).
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Change from baseline to each time point of measurement in vital signs (supine
BP and pulse rate) after study treatment administration.
- Change from baseline to each time point of measurement in ECG variables: HR,
and the intervals: PR, QRS, QT, QTc calculated according to Bazett*s correction
(QTcB), and QTc calculated according to Fridericia*s correction (QTcF) after
study treatment administration.
- Change from baseline to each time point of measurement in clinical laboratory
variables after study treatment administration.
- Change from baseline to EOS in body weight.
- Treatment-emergent ECG abnormalities from study treatment administration up
to EOS.
- Treatment-emergent AEs from study treatment administration up to EOS.
- Treatment-emergent SAEs from study treatment administration up to EOS.
- Mass balance (Cumulative excretion of radioactivity in urine, feces, and
expired air (if applicable))
- PK of 14C radioactivity in whole blood and plasma.
- PK of cenerimod and its metabolites in plasma.
- Metabolic profiling (profiles, identification, and quantification of
cenerimod metabolites in plasma, urine, and feces).
Secondary outcome
Not applicable
Background summary
Cenerimod (also known as ACT-334441) is a new investigational compound that may
eventually be used for the treatment of several autoimmune disorders such as
systemic lupus erythematosus (SLE) or disorders ensuing from organ
transplantation. The immune system is normally the first line of defense
against illness and bad health. However, sometimes immune systems function
abnormally due to deficiencies and disorders where the body either loses its
natural immunity or the immune system turns against the body it is supposed to
protect: these are called autoimmune diseases.
The study compound reduces the amount of specific types of white blood cells (T
and B lymphocytes) in the blood, and thus at the sites of inflammation where
they would usually act, by modulating a specific receptor (sphingosine
1-phosphate receptor 1, S1P1) involved in the release of white blood cells in
the system. Cenerimod is in development and 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
cenerimod is absorbed, distributed, metabolized (broken down) and eliminated
from the body (this is called pharmacokinetics).
Study design
The study will consist of 1 period during which the volunteer will stay in the
clinical research center in Groningen for 23 days (22 nights).
The volunteer will leave the clinical research center in the morning of Day 22.
The volunteer may be required to come back to the clinical research center in
Groningen for a maximum of 7 additional visits (extended observation period)
which will be 24 hours for each visit.
The participation of the volunteer in the extended observation period will
depend on the amount of radioactivity left in his urine, feces, and expired air
at the end of the in-clinic stay (Day 22). This amount of radioactivity will be
measured after Day 22 and before the first planned 24-hour stay of the extended
observation period.
- If the radioactivity recovered during these 22 days meets the pre-defined
stopping criteria for continuing participating in the study, the volunteer will
not be required to come back to the clinical research center for the extended
observation period, but you will be asked to come back for the post-study
screening visit (see below).
- If the radioactivity recovered during these 22 days does not meet the
pre-defined stopping criteria, the volunteer will be required to come back to
the clinical research center for the extended observation period. These visits
are planned on Days 28, 35, 42, 49, 63, 77, and 98. The volunteer will leave
after each 24-hour stay (respectively on Days 29, 36, 43, 50, 64, 78 and 99).
The participation of the volunteer in the extended observation period will end
as soon as the radioactivity recovery meets the pre-defined stopping criteria
(this means that the volunteer may not be required to come to the clinical
research center 7 times). The volunteer will then be asked to come back only
for the post-study screening visit.
Intervention
The volunteer will receive a single dose of 2 mg/3.7 MBq radiolabeled cenerimod
as an oral solution of 25 mL.
Study burden and risks
In this study radiolabeled cenerimod will be used. The amount of radioactivity
in this dose will be approximately 3.7 MBq (MBq = megaBecquerel, this is a unit
to express the amount of radioactivity in the study compound). The average
environmental background radiation burden in The Netherlands is approximately 2
mSv per year (mSv = milliSievert, this unit 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 approximately 3.7 MBq radiolabeled cenerimod is calculated to
be 0.26 mSv. This is approximately 13% of the average annual radiation burden
in the Netherlands.
All potential drugs cause adverse effects; the extent to which this occurs
differs. Cenerimod has been given to 64 healthy volunteers as single doses (up
to 25 mg) and as multiple doses for 35 days (up to 4 mg once daily) as well as
to 36 patients (up to 2 mg once daily) for 12 weeks. The most frequently
observed adverse effects in man were: decreases of blood pressure and pulse
rate with a maximal effect between 4 and 8 hours and which resolved within 12
hours after administration, a transient elevation of liver enzymes when the
study compound was given as multiple dose, and one event of mild dyspnea
(shortness of breath) which also occurred after multiple dosing. One healthy
volunteer suffered from a severe circulatory collapse after a single dose of 25
mg, which was treated using the standard care for circulatory shock. In this
study a dose of 2 mg will be given. subjects should be aware that the
aforementioned adverse effects and possibly other, still unknown adverse
effects, may occur during the study. However, with the dose used in this study
no serious adverse effects are expected. Potential adverse "effects" of
catheter insertion, venipuncture and ECG electrodes are infection of injection
site or rash. No risk of radiation illness are expected with he current
radiation burden.
Gewerbestrasse 16
Allschwil CH-4123
CH
Gewerbestrasse 16
Allschwil CH-4123
CH
Listed location countries
Age
Inclusion criteria
healthy male subjects
45-65 yrs, inclusive
BMI : 18.0-30.0 kg/m2, inclusive
SBP 100-145 mmHg, DBP 50-90 mmHg, and heart rate 55-90 bpm
Signed informed consent in a language understandable to
the subject prior to any study-mandated procedure.
No clinically significant findings on the physical
examination at screening.
Regular (daily) defecation pattern.
Exclusion criteria
No cardiac significant disorders, no asthma, no chronic obstructive pulmonary disease, no tuberculosis. No HIV, hepatitis B and C. No immunosuppressive treatment within 6 weeks. No other investigational drug within 3 months or not more than 4 studies with investigational drugs within 1 year. No study with a radiation burden of >0.1 mSv and =<1 mSv within 1 year (add 1 msv per year).
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 | EUCTR2016-000192-25-NL |
| CCMO | NL58500.056.16 |