In this study we will investigate how safe specific doses of the compound paltusotine are and how well these are tolerated when they are used by healthy participants.We also investigate how much of the compound is broken down and absorbed in the…
ID
Source
Brief title
Condition
- Other condition
- Endocrine disorders congenital
- Endocrine and glandular disorders NEC
Synonym
Health condition
Pituitary Gland disorder (acromegaly)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the safety and tolerability of single doses of paltusotine starting
at 80 mg up to a maximum of 240 mg
Secondary outcome
To evaluate the PK of single doses of paltusotine
Background summary
Paltusotine is administered orally and acts on a receptor called the
somatostatin receptor subtype 2. This receptor type is a target for a number of
currently approved injectable drugs to treat conditions like acromegaly and
neuroendocrine tumors. Acromegaly is a hormonal disorder resulting from the
production of too much growth hormone. Too much growth hormone causes bones to
increase in size, including the hands, feet and face. Paltusotine is an
investigational drug that inhibits growth hormone release and could be a
potential candidate for the treatment of acromegaly.
Paltusotine, like other substances that act on the somatostatin receptor, is
also expected to be a potential candidate for the treatment of neuroendocrine
tumors. Neuroendocrine tumors are caused by tumors usually found in the liver
or the gut. Sometimes, these tumors can secrete substances such as serotonin
and other vasoactive substances. Symptoms most commonly include cutaneous
flushing, and recurrent watery diarrhea and cramping.
Study objective
In this study we will investigate how safe specific doses of the compound
paltusotine are and how well these are tolerated when they are used by healthy
participants.
We also investigate how much of the compound is broken down and absorbed in the
bloodstream of the body (this is called pharmacokinetics).
Participants will receive paltusotine or placebo. A placebo is a compound
without any active ingredient. Please note that when the term *study compound*
is used in this document, we mean paltusotine, placebo, or both.
Paltusotine has been used by humans in a research setting before. In
addition, it has been extensively tested in the laboratory and on animals.
Paltusotine will be tested at various dose levels in this study.
For this study we are looking for up to 27 healthy males and females. The
participants will be divided into 3 different groups (9 participants per
group). You will participate in 1 of these groups.
Study design
Screening -> Day -28 up to Day -3
In-house stay -> Day -2 to Day 3
Visit -> Day 5
Follow-up visit -> Day 8
Subjects will be given paltusotine or placebo as an oral solution of 40
milliliters (mL), 80 mL or less, or 120 mL or less. After administration of the
study compound, the vial will be rinsed twice with 50 mL of water, which they
will also be required to drink. Thereafter they are also required to drink an
additional amount of 100 mL, 60 mL or more, or 20 mL or more of water so that
the total ingested volume will be 240 mL in total (eg, 40 mL study
compound+(2x50 mL water)+100 mL water=240 mL, approximately 1 cup). They will
be required to drink the total 240 mL within 2 minutes. To mask the taste of
both oral solutions, paltusotine or placebo, peppermint strips will be used
before and after solution intake.
Whether they will receive paltusotine or placebo will be determined by chance
and they will not have a choice as to whether they receive paltusotine or
placebo. Per group, 6 participants will receive paltusotine and 3 participants
will receive placebo. Neither the subject, nor the investigators know if
paltusotine or placebo will be administered; we call this a double-blinded
study. However, if it is important for their health, for example in case of a
serious side effect, this information can be looked up during the study.
For safety reasons, initially 2 participants will receive the study compound in
each group. One participant will receive paltusotine, and 1 will receive
placebo. After administration, the safety and tolerability of the study
compound in these 2 participants will be closely monitored. If there are no
concerns about the safety and tolerability within 24 hours after
administration, then the remaining 7 participants (5 will receive paltusotine
and 2 will receive placebo) in the same group will receive the study compound.
Intervention
Group | Treatment | How often
1 | paltusotine 80 mg (oral solution of 40 mL) or placebo | once daily on Day 1
2 | paltusotine 160 mg (oral solution of 80 mL) or lower* or placebo | once
daily on Day 1
3 | paltusotine 240 mg (oral solution of 120 mL) or lower* or placebo | once
daily on Day 1
* In case the dose level will be lower than planned, subjects will be informed
verbally.
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 if necessary 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.
Study burden and risks
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 take about 87 milliliters (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 (small, plastic patches) will be placed on
arms, chest, and legs. To monitor your heart activity, electrodes (small,
plastic patches) will be placed on the chest and abdomen. Prolonged use of
these electrodes can cause skin irritation (rash and itching).
Fasting
If they 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 them to gag. When the sample is taken from the back of the
nose, they may experience a stinging sensation and the eyes may become watery.
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Age
Inclusion criteria
1. Sex: male or female.
2. Age: 18 to 55 years, inclusive, date of signing informed consent.
3. Body mass index (BMI): 18.0 to 30.0 kg/m2, inclusive, date of signing
informed consent.
4. Body weight: >=62.5 kg for Group 3 only.
5. Status: healthy subjects.
6. At screening, female subjects may be of childbearing potential but not
pregnant or lactating, or they may be of nonchildbearing potential (either
surgically sterilized or physiologically incapable of becoming pregnant, or at
least 1 year postmenopausal [amenorrhea duration of 12 consecutive months]);
nonpregnancy will be confirmed for all female subjects by a negative serum
pregnancy test conducted at screening, admission to the clinical research
center, and at the follow-up visit,
7. Female subjects of childbearing potential who have a fertile male sexual
partner must agree to use adequate contraception from at least 12 weeks prior
to administration of the study drug until 90 days after the follow up visit.
Adequate contraception is defined as using hormonal contraceptives or an
intrauterine device combined with at least 1 of the following forms of
contraception: a diaphragm, a cervical cap, or a condom. Total abstinence from
heterosexual intercourse, in accordance with the lifestyle of the subject, is
also acceptable.
8. Male subjects, if not surgically sterilized, must agree to use adequate
contraception and not donate sperm from admission to the clinical research
center until 90 days after the follow-up visit. Adequate contraception for the
male subject (and his female partner, if she is of childbearing potential) is
defined as using hormonal contraceptives or an intrauterine device combined
with at least 1 of the following forms of contraception: a diaphragm, a
cervical cap, or a condom. Total abstinence, in accordance with the lifestyle
of the subject, is also acceptable.
9. All prescribed medication must have been stopped at least 30 days prior to
admission to the clinical research center. An exception is made for hormonal
contraceptives, which may be used throughout the study. Another exception is
made for SARS-CoV-2 vaccines, which are allowed up to 2 weeks prior to
admission to the clinical research center.
10. All over-the-counter medication, vitamin preparations and other food
supplements, or herbal medications (eg, St. John*s wort) must have been stopped
at least 30 days prior to admission to the clinical research center. An
exception is made for paracetamol, which is allowed up to admission to the
clinical research center.
Further criteria apply, see protocol.
Exclusion criteria
1. Employee of PRA or the Sponsor.
2. History of relevant drug and/or food allergies.
3. Smoking more than 5 cigarettes, 1 cigar, or 1 pipe daily; the use of tobacco
products in the 48 hours (2 days) prior to admission to the clinical research
center is not allowed.
4. History of alcohol abuse or drug addiction (including soft drugs like
cannabis products) in the last year.
5. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines
[including ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic
antidepressants, and alcohol) at screening and admission to the clinical
research center.
6. Average intake of more than 21 units of alcohol per week (1 unit of alcohol
equals approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits).
7. Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus
(HCV) antibodies, or human immunodeficiency virus (HIV) 1 and 2 antibodies.
Subjects with previous hepatitis C infection that is now cured may be eligible.
8. Participation in a drug study within 30 days prior to drug administration in
the current study. Participation in 4 or more other drug studies in the 12
months prior to drug administration in the current study.
9. Participation in any previous clinical study with paltusotine.
10. History of hypersensitivity reactions to any excipients in the study drug.
Further criteria apply, see protocol.
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 | EUCTR2021-005883-22-NL |
| CCMO | NL79847.056.21 |