The purpose of this study is to investigate how quickly and to what extent HDM201 is absorbed, broken down and eliminated from the body (this is called pharmacokinetics). HDM201 will be labeled with 14-carbon (14C) and is thus radioactive. In this…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the routes and rates of excretion of [14C]HDM201 related
radioactivity, including mass balance of total drug-related radioactivity in
urine,
feces, and excretion of radioactivity via expired air, following the
administration of a single 25 mg oral dose of [14C]HDM201 in healthy subjects.
To determine the PK of total radioactivity in blood and plasma.
To characterize the single dose plasma PK of HDM201 and/or known key
metabolite(s) if applicable.
Secondary outcome
To evaluate the safety and tolerability of a single 25 mg oral dose of
[14C]HDM201 administered in healthy male and/or female subjects.
Background summary
HDM201 is a new compound that may eventually be used for the treatment of
cancer. p53 is a protein that controls the expression of a large number of
genes involved in DNA repair, apoptosis (programmed cell death), and stopping
the cell cycle. Approximately half of all cancers have inactivated p53 which is
caused by a mutation (change in DNA). HDM201 leads to p53 activation which
leads to an increase in p53 and thereby HDM201 can inhibit the cell growth. The
effect of HDM201 on p53 is seen as a way to treat various types of cancers.
Study objective
The purpose of this study is to investigate how quickly and to what extent
HDM201 is absorbed, broken down and eliminated from the body (this is called
pharmacokinetics). HDM201 will be labeled with 14-carbon (14C) and is thus
radioactive. In this way HDM201 can be traced in blood, urine, feces, and
expired air. HDM201 has been administered to humans before. It has also been
previously tested in the laboratory and on animals.
It will also be investigated how safe the new compound HDM201 is and how well
it is tolerated when it is administered to healthy volunteers.
Furthermore, the effect of your genetic information on your body*s response to
HDM201 will be investigated (this is called pharmacogenetics). This part of the
study is optional.
Study design
The volunteer will once receive 25 milligram (mg) of 14C-labeled HDM201 as an
oral capsule with 240 milliliters (mL) of (tap) water. This amount contains 3.7
MBq (100 µCi) radioactivity. One of the investigators will inspect the
volunteers hands and mouth after intake of the study treatment, to check
whether you have actually taken the study treatment. All subjects will receive
the same study treatment.
Intervention
The volunteer will once receive 25 milligram (mg) of 14C-labeled HDM201 as an
oral capsule with 240 milliliters (mL) of (tap) water. This amount contains 3.7
MBq (100 µCi) radioactivity.
Study burden and risks
The study treatment may cause side effects.
So far, a total of 383 subjects have been treated with HDM201 (331 patients and
52 healthy volunteers) in 7 completed or ongoing studies (6 studies with
patients and 1 study with healthy volunteers) as monotherapy or together with
other drugs.
The most common side effects considered related to the study treatment were:
- Hematological (blood related) side effects:
- Anemia (decrease in the amount of red blood cells or hemoglobin in the blood,
or a lowered ability of the blood to carry oxygen)
- Leukopenia (decrease in the amount of white blood cells in the blood)
including neutropenia (abnormally low concentration of neutrophils [a type
of white blood cells] in the blood)
- Thrombocytopenia (abnormally low concentration of thrombocytes, also known as
platelets, in the blood)
- Gastrointestinal (stomach and gut related) side effects:
- Nausea
- Vomiting
- Diarrhea
- Decreased appetite
- Fatigue
- Rash
The side effects were overall manageable and generally mild to moderate in
severity.
The study treatment may also have side effects that are still unknown.
Possible discomforts due to procedures
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, we will take up to 500 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.
To make a heart tracing, electrodes will be pasted at specific locations on
your arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation.
A sample for the coronavirus test will be taken from the back of the nose and
throat using a swab. Taking the sample only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
your throat may cause the volunteer to gag. When the sample is taken from the
back of the nose, the volunteer may experience a stinging sensation and the
eyes may become watery.
Lichtstrasse 35
Basel 4056
CH
Lichtstrasse 35
Basel 4056
CH
Listed location countries
Age
Inclusion criteria
Healthy males and/or females age 18 to 54 years included
Weighy at least 55 kg and no more than 120 kg
BMI 18.0 - 30 kg/m2
Exclusion criteria
Females of childbearing potential (WOCBP).
Exposure to radiation at a level of 0.1 to1.0 mSv over the past year, 1.1 to
2.0 mSv over the past 2 years, or 2.1 to 3.0 mSv over the past 3 years, etc.,
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.
Use of other investigational drugs within 5 half-lives, or within 6 months (in
case of therapeutics with expected long half-lives such as immunoglobulin G
antibodies), or within 30 days prior to dosing (for
small molecule drugs with daily dosing scheme), or longer if required
by local regulations.
Any surgical or medical condition which might significantly alter the ADME of
drugs, or which may jeopardize the subject in case of participation in the
study.
Has absence of regular defecation pattern (subjects with a mean defecation
frequency of less than once per 2 days or chronic diarrhea).
Positive for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV),
and/or human immunodeficiency virus (HIV).
Smokers (use of tobacco/nicotine products in the previous 3 months).
History or presence of clinically significant ECG abnormalities or a family
history or presence of prolonged QT-interval syndrome.
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 | EUCTR2019-000472-42-NL |
| CCMO | NL72933.056.20 |