In this study we will investigate how quickly and to what extent PHA-022121 is absorbed, transported, and eliminated from the body (this is called pharmacokinetics). PHA-022121 will first be given as a single oral dose, and then as an infusion in a…
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part 1:
The primary objective of this study is to characterize the absorption,
metabolism and excretion of orally administered radiolabeled PHA-022121 in
healthy male subjects.
Part 2:
The primary objective is to determine the absolute bioavailability of orally
administered PHA-022121 in healthy male subjects.
Secondary outcome
Part 1:
The secondary objective of this study is to evaluate safety and tolerability of
a single oral dose of radiolabeled PHA-022121 administered in healthy male
subjects.
Part 2:
The secondary objectives are
- To evaluate the safety and tolerability of simultaneously administered
unlabelled (orally) and radiolabeled (intravenously) PHA-022121 in healthy
male subjects.
- To determine the mass balance after an intravenously (IV) dose of a
microdose/microtracer dose of PHA-022121.
Optional after the results of study PHA022121-C003 and the mass balance data
after IV dosing of a microdose/microtracer dose of PHA-022121 are available:
- To characterize the metabolism of intravenously administered radiolabeled
PHA-022121 in healthy male subjects.
Background summary
PHA-022121 is a new compound that may potentially be used for the treatment of
hereditary angioedema. With this disease, swellings occur (edema), most
commonly in the limbs, the face (lips and tongue), the intestinal tract, the
area of the abdomen near the urinary tract and genitals, and the airways. These
swellings often lead to discomfort, pain, and nausea, and can become life
threatening in case of airway blockade. It is estimated that
hereditary angioedema affects on average 1 in every 50,000 people. PHA-022121
is able to influence a certain receptor, called bradykinin B2, and thereby has
the ability to treat hereditary angioedema.
Study objective
In this study we will investigate how quickly and to what extent PHA-022121 is
absorbed, transported, and eliminated from the body (this is called
pharmacokinetics). PHA-022121 will first be given as a single oral dose, and
then as an infusion in a vein. The dose of PHA-022121 that is administered in a
vein is radioactively labelled with carbon 14 (14C). In this way, PHA-022121
can be traced in blood, urine, and feces. We will also compare the
pharmacokinetics of both administrations.
We also investigate how safe the new compound PHA-022121 is and how well it is
tolerated when it is used by healthy male participants.
We also look at the effect of genetic information on the body*s response to
PHA-022121. The responses to medicines can strongly vary among people and this
may be explained by different genetic profiles. This part of the study is
mandatory.
PHA-022121 has been used by humans before in previous drug studies. In
addition, it has been extensively tested in the laboratory and on animals.
PHA-022121 will be tested at a dose level of 20 milligram (mg).
Study design
The study will take a maximum of 5 weeks (Part 1) or 4 weeks (Part 2) from the
screening until the end of study. For the study it is necessary that subjects
stay in the research for 1 period of 5 days (4 nights) (Part 1) or 7 days (6
nights) (Part 2).
Day 1 is the day when subjects receive the study compound. Subjects are
expected at the research center the day before the day of administration of the
study compound. Subjects will leave the research center on Day 4 (Part 1) or
Day 6 (Part 2) of the study.
Screening visit: Day -21 up to Day -2
Arrival: Day -1
Administration of study compound: Day 1
In-house stay: Day -1 up to Day 4 (Part 1) or Day 6 (Part 2)
Departure and follow-up: Day 4 (Part 1) or Day 6 (Part 2)
Intervention
Part 1:
Subjects will be given PHA-022121 as a drink of 0.4 mL. Because of the small
volume, the drink will be administered via a syringe into the mouth. This will
be followed by drinking 240 milliliters (mL) of water.
Subjects will receive the study compound in the morning after they have fasted
for at least 10 hours (overnight). After intake of the study compound, fasting
continues for 4 more hours.
Subject will receive a single dose of 20 mg 14C-labeled radioactive PHA-022121
one time.
Part 2:
The first dose of PHA-022121 will be given as a drink. Because of the small
volume, the drink will be administered with a syringe into the mouth. This will
be followed by drinking 240 milliliters (mL) of water.
The second dose of PHA-022121 will be radioactively labeled and is given 75
minutes after the first dose. This dose will be given as an intravenous
infusion. The infusion takes 15 minutes.
Subjects will receive PHA-022121 twice:
1. 20 milligram PHA-022121 as a drink.
2. 20 microgram of 14C-labeled radioactive PHA-022121 with a total volume of 8
milliliter that will be given as an intravenous infusion.
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,
seating, low heart rate, or drop in blood pressure with dizziness or fainting.
In total, we will take approximately 321 mL (Part 1) or 359 mL (Part 2) 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 will be placed on arms, chest and legs.
Prolonged use of these electrodes can cause skin irritation.
Meals/Fasting
If subjects 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.
J.H. Oortweg 21
Leiden 2333 CH
NL
J.H. Oortweg 21
Leiden 2333 CH
NL
Listed location countries
Age
Inclusion criteria
1. Subject must be a healthy male, between 18 to 65 years of age, extremes
included, at screening.
2. Subject must have a body mass index (BMI; weight in kg divided by the square
of height in meters) between 18.0 and 30.0 kg/m2, extremes included, and a body
weight not less than 50.0 kg, inclusive, at screening.
3. Subject must sign an ICF indicating that he understands the purpose of the
study including the procedures required, and is willing to participate in the
study, including that he agrees to provide DNA samples for research, before
starting of any screening activities.
4. During the study and for a minimum of 1 spermatogenesis cycle (defined as up
to and including 90 days after receiving the study drug), a male subject may be
enrolled if he is willing and able to adhere to the contraceptive requirement
as specified in 4.5 item 12 in the protocol.
5. Subject must be willing and able to adhere to the prohibitions and
restrictions.
Further criteria apply.
Exclusion criteria
1. Subject has a history of current clinically significant medical illness
including (but not limited to) cardiac arrhythmias or other cardiac disease,
hematologic disease, lipid abnormalities, significant pulmonary disease,
including bronchospastic respiratory disease, diabetes mellitus, hepatic or
renal insufficiency (estimated creatinine clearance < 61 mL/min/1.73m2 at
screening, calculated by MDRD formula), thyroid disease, neurologic or
psychiatric disease, infection, or any other illness, that in the
investigator*s and/or sponsor*s medical monitor opinion should exclude the
subject or that could interfere with the interpretation of the study results.
2. Subject has one of the following laboratory abnormalities at screening as
defined by the National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events (CTCAE) version 5.0, 27 November, 2017 and in accordance with
the normal ranges of the clinical laboratory if no gradings are available.
- Serum creatinine elevation grade 1 or greater (>1.1 x upper limit of normal
range [ULN])
- Hemoglobin below LLN (reference of site);
- Platelet count below LLN;
- Absolute neutrophil count lowering grade 1 or greater (<=1,5 109/L );
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >=ULN;
- Total bilirubin>=ULN;
- Any other toxicity grade 2 or above, except for grade 2 elevations for
triglycerides, low density lipoprotein (LDL) cholesterol and/or total
cholesterol.
3. Clinically significant abnormal values for hematology, clinical chemistry or
urinalysis at screening or at admission to the clinical site on Day -1 as
deemed appropriate by the investigator.
4. Subject, at screening, has a positive test of human immunodeficiency virus
(HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C
antibodies.
5. Subject has a history of heart arrhythmias , tachycardia at rest or history
of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family
history of long QT syndrome).
Further criteria apply.
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 | EUCTR2020-006083-83-NL |
| CCMO | NL76529.056.21 |