Elinzanetant is an investigational compound. It is not approved for sale. That means it can only be used in studies like this one. Elinzanetant has been extensively tested in the laboratory. It has also been already administered to approximately 300…
ID
Source
Brief title
Condition
- Menopause related conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate the effect of multiple doses of esomeprazole on the PK of
elinzanetant
Secondary outcome
To investigate the safety and tolerability of elinzanetant
To determine the absolute bioavailability of elinzanetant after single oral
administration of elinzanetant together with an IV microtracer dose of
[13C5]BAY3427080
Background summary
Elinzanetant is a new compound that may potentially be used for the treatment
of postmenopausal vasomotor symptoms (VMS; hot flashes and night sweats).
During the menopause, the amount of estrogen in the blood decreases. Research
shows that this affects the brain center that regulates body temperature.
Elinzanetant blocks a chemical in the brain (neurokinin 1 and 3) that is
involved in the regulation of the body temperature. This could lead to
effective treatment of VMS in postmenopausal women.
Study objective
Elinzanetant is an investigational compound. It is not approved for sale. That
means it can only be used in studies like this one. Elinzanetant has been
extensively tested in the laboratory. It has also been already administered to
approximately 300 healthy males and females in 10 clinical trials.
In this study we investigate the influence of the acidity in the gastro
intestinal tract on how quick and to what extent elinzanetant is processed by
the body (this is called pharmacokinetics). We will also investigate how safe
the compound is and how well it is tolerated when it is used by healthy
participants alone and in combination with esomeprazole.
Esomeprazole been used by patients for over 20 years for the treatment of
reflux and peptic ulcers. In this study, the acidity in the gastro intestinal
tract will be changed (made less acidic) with esomeprazole to see if this
affects how elinzanetant is processed by the body.
The processing of elinzanetant administered as capsules will also be compared
to the processing of elinzanetant administered as intravenous (iv; in the vein)
infusion. The iv infusion of elinzanetant is a very low dose. The elinzanetant
in the infusion is also made heavier by adding a carbon-13 atom to it.
Carbon-13 is called an isotope and is not radioactive. This makes it possible
to compare the amount of elinzanetant which is administered via the infusion
with the amount administered as capsules and how both are processed by the
body.
Study design
The study will take a maximum of 10 weeks from the screening until the
follow-up visit.
For the study it is necessary that the volunteer stays in the research center
for 21 days (20 nights).
The volunteer will be given elinzanetant as oral capsules with 240 milliliters
(mL) of water and as an intravenous infusion. Esomeprazole will be given as
oral tablets with 240 mL of water.
During the first hour after administration of the study compound on Day 1 and
Day 13 the volunteer is not be allowed to lie down (except when instructed to
do so by one of the investigators), as this may influence the uptake of the
study compound.
On Day 13, the dose of esomeprazole is given very early: around 6 o*clock in
the morning.
Intervention
Day | Treatment | Route | Timing | How often
1 | Elinzanetant 120 mg (2x60 mg soft gelatin capsules) | oral | Morning | once
| [13C5]Elinzanetant 100 µg in 10 mL over 30 minutes | intravenous
infusion | 1 hour after oral administration | once
9-13 | Esomeprazole 40 mg (1 tablet) | oral | Morning | once daily
13 | Elinzanetant 120 mg (2x60 mg soft gelatin capsules) | oral | 3 hours after
esomeprazole | once
Study burden and risks
Possible side effects:
The study compound may cause side effects
Elinzanetant has already been studied in approximately 510 persons,
approximately 300 healthy persons and 210 patients with
troublesome-postmenopausal VMS (hot flashes and night sweats) and other
conditions. The following side effects are very often observed (in 1 in 10
people or more):
- Somnolence
- Fatigue
- Dizziness
- Constipation
The study compound may also have (serious) side effects that are still unknown.
In addition to unknown side effects, there is a (small) chance that an allergic
reaction will occur. This can be caused by the study compound or other
ingredients that are used to prepare the formulation.
Esomeprazole may also cause side effects. The most important ones are:
- Headache
- Abdominal pain
- Diarrhea
- Nausea
Possible Discomforts:
Blood draw
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula (a tube in a vein in the arm) 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, seating, low heart rate, or drop in blood
pressure with dizziness or fainting.
In total, we will not take more than 500 milliliters (mL) of blood from the
volunteer. 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 may be more than the amount indicated above.
Heart tracing
To make a heart tracing, electrodes (small, plastic patches) will be placed on
the volunteer his arms, chest and legs. Prolonged use of these electrodes can
cause skin irritation (rash and itching).
Coronavirus test
Samples for the coronavirus test will be taken from the back of the volunteer
his 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 volunteer his throat may cause him to gag. When the sample
is taken from the back of the volunteer his nose, he may experience a stinging
sensation and his eyes may become watery.
Kaiser-Wilhelm-Allee 1
Leverkusen 51386
DE
Kaiser-Wilhelm-Allee 1
Leverkusen 51386
DE
Listed location countries
Age
Inclusion criteria
1. Participant must be 18 to 65 years of age inclusive, at the time of signing
the informed consent.
2. Participants who are overtly healthy as determined by medical evaluation
including medical history, physical examination, laboratory tests, and cardiac
monitoring.
3. Body weight of at least 50 kg and body mass index (BMI) within the range of
18.0 to 30.0 kg/m^2 (inclusive).
4. Male and female
Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies.
- Male participants: Male participants of reproductive potential must agree to
use a condom (with or without spermicide) when sexually active. This applies
for the time period between the signing of the
informed consent form (ICF) until 5 days after the last dose of study
intervention. Female partners of childbearing potential of male participants do
not need to follow special precautions.
- Female participants: Women of childbearing potential will have to use highly
effective non-hormonal contraception when having sexual intercourse with a male
partner from signing the ICF until 5 days after last dose of the study drug.
-- Women of non-childbearing potential are not required to use contraception.
Non-childbearing potential is defined as
- Postmenopausal state confirmed by follicle stimulating hormone (FSH) level
>33.4 U/L, or above reference range from the local laboratory, or
- Surgically sterilized by bilateral tubal ligation, bilateral oophorectomy
with or without hysterectomy, or hysterectomy documented by medical report
verification.
Exclusion criteria
1. Any clinically relevant abnormal findings in medical history and physical
examination which in the opinion of the investigators, may put the participant
at risk because of his/her participation in the trial or provide difficulties
in interpreting the trial data.
2. History or evidence of any clinically relevant cardiovascular,
gastrointestinal, endocrine, hematologic, hepatic, immunologic, metabolic,
urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other
clinically relevant disease, as judged by the investigator.
3. Pre-existing diseases for which it can be assumed that the absorption,
distribution, metabolism, elimination and effects of the study intervention
will not be normal.
4. Any medical disorder, condition or history of such that would impair the
participant's ability to participate or complete this study in the opinion of
the investigator.
5. Known hypersensitivity to the study interventions (active substances, or
excipients of the preparations).
6. Known severe allergies e.g., allergies to more than 3 allergens, allergies
affecting the lower respiratory tract - allergic asthma, allergies requiring
therapy with corticosteroids, urticaria or significant nonallergic drug
reactions.
7. Relevant diseases within the last 4 weeks prior to the first study
intervention administration.
8. Febrile illness within 4 weeks before first study intervention
administration.
9. Contraindications for the use of esomeprazole, especially known hereditary
problems of fructose intolerance, glucose-galactose malabsorption or
sucrase-isomaltase insufficiency
10. Use of drugs which may affect absorption (e.g. loperamide, metoclopramide)
within 1 week before first study drug administration.
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 | EUCTR2021-002032-24-NL |
| CCMO | NL78829.056.21 |