In this study we will investigate how safe the new compound seltorexant is and how well it is tolerated when it is used by healthy participants.We also investigate how quickly and to what extent seltorexant is absorbed, transported, and eliminated…
ID
Source
Brief title
Condition
- Sleep disturbances (incl subtypes)
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the absolute bioavailability of seltorexant in healthy
participants following a single oral dose of seltorexant and an IV infusion
dose of 14C-seltorexant.
endpoint: Absolute bioavailability calculated as the ratio of dose normalized
AUC of oral and IV administration.
Secondary outcome
To evaluate the PK of seltorexant in healthy participants following a single
oral dose of seltorexant and an IV infusion dose
of 14C-seltorexant. endpoint: Pharmacokinetic parameters: AUC, Cmax, Tmax, and
half-life
To assess the safety and tolerability of a single oral dose of seltorexant and
an IV infusion dose of 14C-seltorexant.
endpoint: adverse events
Background summary
Seltorexant is a new compound that may potentially be used for the treatment
of sleeplessness and depression. Seltorexant binds to the orexin-2 receptor and
inhibits it. This receptor is present in the brain of humans. From research it
is known that the orexin-2 receptor is important in patients with depression
and insomnia. So far 23 studies have been done on seltorexant with a total of
1,355 persons. These persons include healthy participants, patients with
depression, patients with sleeplessness, patients with both depression and
sleeplessness, patients with obstructive sleep apnea and a patient with renal
impairment. There are indications that seltorexant can cause a decrease in
depressive symptoms, increases sleeping time and makes falling asleep easier.
Study objective
In this study we will investigate how safe the new compound seltorexant is and
how well it is tolerated when it is used by healthy participants.
We also investigate how quickly and to what extent seltorexant is absorbed,
transported, and eliminated from the body after oral as well as after
intravenous administration. For this study, seltorexant is labelled with low
levels of radioactive carbon-14 (14C). In this way seltorexant can be traced in
blood. The additional radiation the participant will be exposed to in this
study is negligible (that is, it is less than the natural background radiation
during 1 month).
We also look at the effect of the genetic information on the body*s processing
of seltorexant. This part of the study is mandatory.
Seltorexant has been used by humans before. In addition, it has been
extensively tested in the laboratory and on animals.
Study design
For the study it is necessary that the participant stays in the research center
for 6 days (5 nights). In addition, participant will be called 1 time 2 days
after the research center is left. Questions will be asked about concomitant
medication and adverse events.
Day 1 is the day when the participant receives the study compound. Participant
will leave the research center on Day 5 of the study
Seltorexant will be administered as an oral tablet with 240 milliliter (mL) of
water in the evening of Day 1, approximately 3 hours after dinner. Dinner may
be given earlier than one is used to, at about 17:00. Two hours after
administration of the oral tablet, 14C-labeled seltorexant will be administered
as an intravenous infusion. The infusion takes approximately 15 minutes.
During the first 4 hours after administration of the study compound as an oral
tablet it is advised to lie down (except when instructed to do not so by one of
the investigators) or to remain seated, as this may influence the uptake of the
study compound.
One of the investigators will inspect the hands and mouth of the participant
after the study compound intake as an oral tablet. This is to check if the
study compound has been taken.
Intervention
Participant will be given seltorexant as an oral tablet with 240 milliliter
(mL) of water in the evening of Day 1, approximately 3 hours after dinner.
Dinner may be given earlier than one is used to, at about 17:00. Two hours
after administration of the oral tablet, participant will receive of
14C-labeled seltorexant as an intravenous infusion. The infusion takes
approximately 15 minutes.
During the first 4 hours after administration of the study compound as an oral
tablet participant will be advised to lie down (except when instructed to do
not so by one of the investigators) or to remain seated, as this may influence
the uptake of the study compound.
On Day 1: Seltorexant as a Tablet, once 3 hours after dinner
On Day 1: 14C-labeled seltorexant in 15 mL as an Intravenous infusion, once
during 15 minutes, 2 hours after administration of seltorexant tablet
Study burden and risks
General:
During the first night after the evening doses, the sleep will be disturbed due
to the group housing and frequent blood draws with necessary lighting.
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, seating, low
heart rate, or drop in blood pressure with dizziness or fainting.
In total, we will take not more than 300 milliliters (mL) of blood from the
participant from screening to leaving the research center. 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 the arms, chest and legs.
Prolonged use of these electrodes can cause skin irritation.
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 the participant to gag. When the sample is taken from the
back of the nose, participant may experience a stinging sensation and the eyes
may become watery.
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
1. 18 to 55 years of age, inclusive.
2. Healthy on the basis of medical history at screening and physical
examination, vital signs,
and 12-lead ECG performed at screening and at admission to the study site on
Day -1.
3. Healthy on the basis of clinical laboratory tests performed at screening and
at admission
to the study site on Day -1. If the results of the clinical chemistry panel,
hematology, or
urinalysis are outside the normal reference ranges, the participant may be
included only
if the investigator judges the abnormalities or deviations from normal to be
not clinically
significant. This determination must be recorded in the participant's source
documents
and initialed by the investigator. One repeat for out-of-range laboratory
values is
permitted.
4. Body weight not less than 50 kg and body mass index (BMI; weight
[kg]/height2 [m]2)
within the range 18 kg/m2 and 32 kg/m2 (inclusive).
5. Man or woman
Exclusion criteria
1. History of or current clinically significant medical illness including (but
not limited to) cardiac arrhythmias or other cardiac disease, hematologic
disease, coagulation disorders (including any abnormal bleeding or blood
dyscrasias), lipid abnormalities, significant pulmonary disease, including
bronchospastic respiratory disease, diabetes mellitus, hepatic or renal
insufficiency (creatinine clearance below 60 mL/min based on Chronic Kidney
Disease Epidemiology Collaboration [CKD-EPI] equation), thyroid disease, kidney
or urinary tract disturbances, neurologic or psychiatric disease like MDD,
generalized anxiety disorder (GAD), psychotic disorders, infection, seizure
disorder, or any other illness that the investigator considers should exclude
the participant or that could interfere with the interpretation of the study
results. Significant past gastrointestinal medical history, or any
disease/surgery (NOTE: cholecystectomy and appendectomy are not exclusionary)
that would interfere with drug absorption.
2. Clinically significant abnormal values for hematology, clinical chemistry,
or urinalysis at screening or at admission to the study site (Day -1) as
determined by the investigator. Alanine transaminase (ALT)/aspartate
transaminase (AST) concentrations within normal range at screening. One retest
for ALT/AST is permitted
3. Clinically significant abnormal physical examination, vital signs, or
12-lead ECG at screening or at admission to the study site on Day -1 as
determined by the investigator.
4.1 Participant has a current or recent history of serious suicidal ideation
within the past 6 months, corresponding to a positive response on item 4
(active suicidal ideation with some intent to act, without specific plan) or
item 5 (active suicidal ideation with specific plan and intent) for ideation on
the Columbia-Suicide Severity Rating Scale (C-SSRS), or a lifetime history of
suicidal behavior or suicidal attempt as validated by the C-SSRS at screening.
5. Positive test for human immunodeficiency virus (HIV)-1 and HIV-2 antibodies,
hepatitis B surface antigen (HBsAg), or hepatitis C antibodies.
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 | EUCTR2021-004068-92-NL |
| CCMO | NL79719.056.21 |