In this study we will investigate how safe the new compound LEO 153339 is and how well it is tolerated when it is used by healthy participants. We also investigate how quickly and to what extent LEO 153339 (and the breakdown product) is absorbed,…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Psoriasis
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the safety and tolerability of LEO 153339 in healthy subjects.
Secondary outcome
To evaluate the pharmacokinetics (PK) of LEO 153339 and LEO 159074
(N-glucuronide metabolite) in healthy subjects.
Background summary
LEO 153339 has not been given to humans before. As LEO 153339 will be given to
humans for the first time in this study, side effects of LEO 153339 in humans
are not known yet. LEO 153339 has been studied extensively in the laboratory
and in animals.
Secukinumab is a compound that has a similar mode of action as LEO 153339. The
most common side effects reported in patients that took secukinumab over 12 and
52 weeks were upper respiratory infections, headache, and diarrhea.
Animal experiments have been done with doses much higher than those planned in
the current study. In an experiment where animals received 600 mg/kg and 400
mg/kg LEO 153339, 3 out of 10 animals showed convulsions. Subjects are also
under strict medical supervision and additional measures are taken, such as
neurological examinations, EEGs, and cognitive tests (Cogstate Safety Battery
test) to make sure that they remain safe from serious effects.
Study objective
In this study we will investigate how safe the new compound LEO 153339 is and
how well it is tolerated when it is used by healthy participants.
We also investigate how quickly and to what extent LEO 153339 (and the
breakdown product) is absorbed, transported, and eliminated from the body. In
addition, in Part 2 we look at the effect of LEO 153339 on immune cells in the
blood.
We also look at the effect of your genetic information on your body*s response
to LEO 153339. We compare the effects of LEO 153339 with the effects of a
placebo.
LEO 153339 has not been given to humans before. It has been extensively tested
in the laboratory and on animals. LEO 153339 will be tested at various dose
levels.
Study design
Part 1
The study will take a maximum of 5 weeks from the screening until the follow-up.
It is necessary that subjects stay in the research center for one period of 6
days (5 nights).
Screening > Day *30 up to Day *3
Arrival > Day *2
In-house stay > Day *2 up to Day 4
Departure > Day 4
Follow-up > Day 4
Subjects will be given LEO 153339 or placebo as oral capsules with 240
milliliters (mL) of (tap) water. One of the investigators will inspect the
hands and mouth after the study compound intake. This it to check if they have
taken the study compound. In one group (Group B1), LEO 153339 can be given as a
cloudy drink (suspension).
Based on emerging data from the study, it may also be decided that the dose
will be given in the form of a cloudy drink (suspension), for example when it
appears that the capsule is not sufficiently absorbed by the body.
Part 2
The study will take a maximum of 6 weeks from the screening until the follow-up.
It is necessary that subjects stay in the research center for one period of 12
days (11 nights).
Screening > Day *30 up to Day *3
Arrival > Day *2
In-house stay > Day *2 up to Day 10
Departure > Day 10
Follow-up > Day 10
Subjects will be given LEO 153339 or placebo as oral capsules with 240
milliliters (mL) of (tap) water. One of the investigators will inspect the
hands and mouth after the study compound intake. This it to check if they have
taken the study compound.
Based on emerging data from the study, it may also be decided that the dose
will be given in the form of a cloudy drink (suspension), for example when it
appears that the capsule is not sufficiently absorbed by the body.
On Day 5, subjects will receive the morning dose of the study compound after
eating a high-fat breakfast with a standard composition. This breakfast must be
started exactly on time and must be finished within 20 minutes. The entire
breakfast must be consumed.
Intervention
Part 1
The study compound will be given once on Day 1.
The table below shows the planned dose levels for each group. The doses of
later groups can be adjusted. For example because the study compound had more
or less effect than was expected. The dose for the next group will only be
increased if the lower dose of the previous group was found to be well
tolerated and in case of no objection by the Medical Research Ethics Committee.
The study will be discontinued or the dose will be decreased if, in the opinion
of the investigators, unacceptable side effects appear.
Group | Treatment* | How often | How
A1 | LEO 153339 10 mg or placebo | Once | Capsule
A2 | LEO 153339 40 mg or placebo | Once | Capsule
A3 | LEO 153339 100 mg or placebo | Once | Capsule
A4 | LEO 153339 200 mg or placebo | Once | Capsule
A5 | LEO 153339 375 mg or placebo | Once | Capsule
A6 | LEO 153339 375 mg or placebo | Once | Cloudy drink
A7 | LEO 153339 750 mg or placebo | Once | Cloudy drink
B1** | LEO 153339 X mg | Once | Cloudy drink
* In case the dose level will be lower or higher than planned, subjects will be
informed verbally.
** Group B1 is only done if needed. All participants will receive LEO 153339
and no participant will receive placebo. The dose that will be used will be
based on the results of the previous groups.
Part 2
The study compound will be given once, twice (12 hours apart), or 4 times daily
(6 hours apart) for 7 days. On the last dosing day (Day 7), only one dose will
be given. The table below shows the planned dose levels for each group. The
doses of later groups can be adjusted. For example because the study compound
had more or less effect than was expected. The dose for the next group will
only be increased if the lower dose of the previous group was found to be well
tolerated and in case of no objection by the Medical Research Ethics Committee.
The study will be discontinued or the dose will be decreased if, in the opinion
of the investigators, unacceptable side effects appear.
Group | Treatment* | How often | How
C1 | LEO 153339 40 mg or placebo | Once, twice or four times daily** | Capsule
C2 | LEO 153339 100 mg or placebo | Once, twice or four times daily** | Capsule
C3 | LEO 153339 250 mg or placebo | Once, twice or four times daily** | Capsule
or cloudy drink
C4 | LEO 153339 500 mg or placebo | Once, twice or four times daily** | Capsule
or cloudy drink
C5 | LEO 153339 800 mg or placebo | Once, twice or four times daily** | Capsule
or cloudy drink
C6 | LEO 153339 1000 mg or placebo | Once, twice or four times daily** |
Capsule or cloudy drink
* In case the dose level will be lower or higher than planned, subjects will be
informed verbally.
** Only 1 dose will be given on the last dosing day (Day 7)
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 (bruising) 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 about 140 (Part 1) or 290 (Part 2) milliliters (mL) of
blood. This amount does not cause any problems in adults. To compare: a blood
donation involves 500 mL of blood being taken 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 will be more than the amount indicated above.
Heart tracing
To make a heart tracing, electrodes will be placed on arms, chest and legs. To
monitor heart rate, electrodes will be placed on chest and abdomen. Prolonged
use of these electrodes can cause skin irritation (rash and itching).
Brain activity (EEG)
We will measure the electrical activity in the brain by making an EEG. For
this, we will place 19 electrodes on different locations on the head (we will
use a cap for this). The electrodes are connected to a machine that determines
the electrical activity. During the EEG subjects should be resting comfortably.
Meals/Fasting
If you have 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 subjects to gag. When the sample is taken from the back of
the nose, subjects may experience a stinging sensation and the eyes may become
watery.
Part 2 only
Meals/Fasting
The high-fat breakfast is a big breakfast containing 2 fried eggs, fried
potatoes, bacon and more. Subjects must consume the whole breakfast. It can be
difficult to consume the entire breakfast, particularly for light eaters.
Industriparken 55
Ballerup DK-2750
DK
Industriparken 55
Ballerup DK-2750
DK
Listed location countries
Age
Inclusion criteria
Healthy adult males and females.
Age between 18 and 65 years (both inclusive) at screening.
A body mass index (BMI) between 18.0 and 32.0 kg/m2 (both inclusive).
In good health at screening and/or check-in (Day -2 and Day -1) as judged by
the investigator based on medical history, physical examination, vital signs,
12 lead ECG, and clinical laboratory evaluations.
Exclusion criteria
Male subjects sexually active with a woman of childbearing potential who are
not willing to use a barrier method of contraception (e.g. condom) from the
time of first dose of IMP until 3 months after the last dose, in conjunction
with this female partner using a highly effective form of contraception. For
vasectomised male subjects, male subjects with a female partner with bilateral
tubal occlusion or ligation, and heterosexually abstinent male subjects (when
this is in line with the
preferred and usual life style of the subject and not just being without a
current partner), no additional contraception is required.
Female subjects who are pregnant, lactating, or of childbearing potential
Any surgical or medical condition or cholecystectomy which might significantly
alter the absorption, distribution, metabolism, or excretion of any drug.
Positive polymerase chain reaction (PCR) test for coronavirus disease 2019
(COVID-19) at Day -2 or Day -1 or within 8 weeks prior to screening or
check-in, or contact with COVID-19 positive (or suspected) persons within 14
days prior to first dose.
Treatment with any prescribed or non-prescribed systemic or topical medication
within 7 days prior to the first dose of IMP (excluding paracetamol; including
herbal remedies), unless, in the opinion of the investigator and the sponsor,
the medication will not interfere with the trial procedures or compromise
safety.
Treatment with any non-marketed drug substance (that is, an agent which has not
yet been made available for clinical use following registration) within 3
months prior to the first dose of IMP.
ECG with QT interval corrected for heart rate using Fridericia's formula (QTcF)
>450 msec confirmed by repeat measurement at screening.
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 | EUCTR2020-005748-51-NL |
| CCMO | NL77226.056.21 |