In this study, we will investigate how quickly and to what extent the study compound MIJ821 is absorbed, transported, and eliminated from the body. For this study, MIJ821 is radioactively labelled with carbon-14 (14C). In this way, MIJ821 can be…
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To determine the routes and rates of excretion of [14C]MIJ821 related
radioactivity, including mass balance of total drug-related radioactivity in
urine, feces, and elimination of radioactivity via expired air, following a
single 0.16 mg/kg 40-minute i.v. infusion of [14C]MIJ821 in healthy male
participants.
- To determine the pharmacokinetics (PK) of total radioactivity radiolabeled
components in blood and plasma following a single 0.16 mg/kg 40-minute i.v.
infusion of [14C]MIJ821 in healthy male participants.
- To characterize the PK of MIJ821 and known key metabolites, if applicable, in
plasma following a single 0.16 mg/kg 40-minute i.v. infusion of [14C]MIJ821 in
healthy male participants.
Secondary outcome
- To assess the safety and tolerability of a single 0.16 mg/kg i.v. dose of
[14C]MIJ821 in healthy male participants.
Background summary
MIJ821 is a new compound that may potentially be used for the treatment of
major depressive disorder. Major depressive disorder is characterized by low
mood and often by low self-esteem, low energy, and a loss of interest. It can
strongly affect a person*s life and health, including significantly increased
risk of suicidality, and is difficult to treat, even with existing
antidepressants. If at least two different types of treatment do not help, this
is considered a treatment resistant depression.
Ketamine has been shown to produce rapid (within hours) and long lasting (days
to weeks) antidepressant effects in patients with treatment resistant
depression, but can result in a dissociative state (a feeling of being
separated from the body, like a trance). The mechanisms of action of MIJ821 is
similar to that of ketamine. However, by acting more specifically than
ketamine, MIJ821 aims to reduce the dissociative side effects, while still
having an antidepressant effect.
Study objective
In this study, we will investigate how quickly and to what extent the study
compound MIJ821 is absorbed, transported, and eliminated from the body. For
this study, MIJ821 is radioactively labelled with carbon-14 (14C). In this way,
MIJ821 can be traced in blood, urine, feces, and expired air. We also look at
the break down products of MIJ821 in urine, feces, and blood.
We will also investigate how safe the new compound MIJ821 is and how well it is
tolerated when it is used by healthy male participants.
We also look at the effect of your genetic information on your body*s response
to MIJ821 as follows:
1) We will analyze your DNA for the activity of a gene of the enzyme called
CYP2D6. Taking part in this DNA test is mandatory.
2) We will do exploratory research to investigate if differences in genetic
information relate to differences in how the body handles MIJ821.Taking part in
this DNA test is not mandatory.
MIJ821 has been used by humans before. In addition, it has been extensively
tested in the laboratory and on animals.
Study design
The research requires the volunteer to stay in the research center for 17 days
(16 nights). Day 1 is the day the study drug is administered.
From Day 1 to Day 16, all urine and faeces are collected and regular blood and
exhaled air samples are taken to measure the amount of radioactivity in the
urine, faeces, blood and exhaled air. If the amount of radioactivity on Day 16
is still above predefined limits, the volunteer should return to the study
center for up to 4 additional 24-hour visits.
For 24 hours prior to entering the research center for the stay and before the
24-hour visits, the volunteer should collect faeces at home and bring them to
the research center.
Below is an overview of the days on which the volunteer stays in the research
center or on which the volunteer visits the research center:
Screening
1 short visit between Day -35 and Day 2
Arrival
Day 1
Inhouse stay
Day -1 to Day 16
Departure
Day 16
The volunteers may need to come back to the research center after their
departure on Day 16. This depends on the amount of radioactivity in the bodily
material.
24-hour visits
Day 18 to Day 19*
Day 22 to Day 23*
Day 27 to Day 28*
Day 33 to Day 34*
*Depending on the radioactivity levels in the bodily material, these visits can
be cancelled
The volunteer receives MIJ821 as an intravenous infusion (solution of the drug
administered directly into a blood vessel). The infusion lasts 40 minutes.
The volunteer will receive the study drug on the morning of Day 1 after a 10
o'clock overnight fast. After administration, the volunteer must fast for
another 4 hours. also, the volunteer should not drink any liquids from 1 hour
before to 2 hours after dosing.
Intervention
The volunteer will receive a single dose of 0.16 mg/kg of 14C radioactively
labeled MIJ821. This means that 0.16 milligram of MIJ821 will be administered
per 1 kg of body weight, so the actual dose will depend on the body weight of
the volunteer. The dose will contain between 0.98 mSv and 1.52 mSv of
radiation, depending on that body weight.
Study burden and risks
Blood draw:
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula can sometimes lead to inflammation, swelling, hardening of the vein,
blood clotting, and bleeding in the environment of the puncture site. In some
individuals, a blood draw can sometimes cause pallor, nausea, sweating, low
heart rate, or drop in blood pressure with dizziness or fainting.
In total, we will take a maximum of 500 mL of blood from screening to
follow-up. This amount does not cause any problems in adults. To compare: a
blood donation involves 500 mL of blood being taken at once each time. If the
investigator thinks it is necessary for the safety of a participant, extra
samples might be taken for possible additional testing. If this happens, the
total amount of blood drawn may be more than the amount indicated above.
Heart tracing:
To make a heart tracing, electrodes will be placed on arms, chest and legs.
Prolonged use of these electrodes can cause skin irritation.
Intravenous infusion of the study compound
The infusion of the study compound in a vein in your arm may result in
reactions in the skin around the place where the needle goes in. Furthermore,
reactions such as itching, flushing, headache, nausea/vomiting, low blood
pressure, urticaria or changes in breathing could occur.
Fasting:
If someone has to fast for a prolonged time during the study, this may lead to
symptoms such as dizziness, headache, stomach upset, or fainting.
Coronavirus test:
Samples for the coronavirus test will be taken from the back of the nose and
throat using swabs. Taking the samples only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause gagging. When the sample is taken from the back of the
nose, The volunteer may experience a stinging sensation and eyes may become
watery.
Lichtstrasse 35
Basel 4056
CH
Lichtstrasse 35
Basel 4056
CH
Listed location countries
Age
Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study.
2. Healthy males, aged 18 to 55 years (inclusive) and in good health as
determined by past and current medical history, physical and neurological
examination, vital signs, electrocardiogram, and laboratory tests at screening
and baseline (whenever applicable).
3. At screening and at baseline (Day -1), vital signs after 5 minutes in supine
position must be within the ranges defined in protocol inclusion
criteria.
4. Participants must weigh at least 60 kg and should not exceed 90 kg to
participate in the study and must have a body mass index (BMI)
within the range of 18.0 to 29.9 kg/m² (inclusive) at screening.
5. NM or IM for CYP2D6.
6. Participants must be able to communicate well with the Investigator and to
comply with the requirements of the entire study, including adhering to study
restrictions and visit schedule.
See protocol for complete details of inclusion criteria.
Exclusion criteria
1. Recent history (<3 months) prior to screening of nicotine product use or a
urine cotinine level >500 ng/mL at Screening or Baseline.
2. Positive blood alcohol concentration or drug test at Screening or Baseline.
3. Absence of regular defecation pattern (participants with an average
defecation frequency of less than once per 2 days or chronic diarrhea).
4. Any surgical or medical condition that might significantly alter the (A)DME
of drugs, or that may jeopardize the participant in case of
participation in the study.
5. Exposure to radiation at a level of up to 1.0 mSv over the past year, or up
to 3.0 mSv over the past 3 years. (e.g., due to systemic
administration of radioactive substances, or to external irradiation [e.g., by
X-rays] for diagnostic, therapeutic, job-related, or research
purposes).
Further criteria apply, see protocol.
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 | EUCTR2021-006026-51-NL |
| CCMO | NL80917.056.22 |