In this study we will investigate how quickly and to what extent a formulation of the study compound PHA-022121 is absorbed, transported, and eliminated from the body. There are two compositions of the study compound: one with an extended release…
ID
Source
Brief title
Condition
- Haematological disorders NEC
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. ECGs
2. vital sign measurements
3. PK blood sampling for PHA-022121 and its metabolites (PK blood sampling
should be kept as close as possible to the specified time points.)
4. safety laboratory samples
Secondary outcome
N/A
Background summary
PHA-022121 is a new compound that may potentially be used for the treatment of
hereditary angioedema. Hereditary angioedema is a rare disease that affects 1
in 50,000 people. The disease has edema attacks in the limbs, face (lips and
tongue), intestinal tract, urinary tract, genital tract, and airways. Attacks
often lead to discomfort, pain, and nausea and can become life threatening if
the airways are blocked, with a 30% risk of suffocation. PHA-022121 can block a
specific protein that plays an important role in how the body handles fluids
and could therefore potentially be beneficial for the treatment of hereditary
angioedema.
The extended release formulation is being developed as an alternative to the
immediate release formulation. With extended release, patients in the future
will have to take the compound less frequently. This makes it easier for
patients to adhere to the treatment.
Study objective
In this study we will investigate how quickly and to what extent a formulation
of the study compound PHA-022121 is absorbed, transported, and eliminated from
the body. There are two compositions of the study compound: one with an
extended release and one with an immediate release. Extended release means that
the active ingredient is not released all at once but is released slowly, after
which it has a long and well-dosed effect. These compositions will be compared
to each other in this study. We also look at breakdown products of PHA-022121.
We will also investigate how safe the new compound PHA-022121 is and how well
it is tolerated when it is used by healthy subjects.
PHA-022121 has been administered to humans before in 7 completed drug studies
and 154 healthy subjects have received at least 1 dose of PHA-022121. In
addition, it has been extensively tested in the laboratory and on animals.
Study design
In total the volunteer will come to the research center 4 times:
• once for the screening as described before.
• 2 times for stays in the research center of 9 days (8 nights) each. In each
period, the volunteer is expected at the research center the day before
administration of the study compound. Day 1 of each period is the day when the
volunteer receives the study compound. The volunteer will leave the research
center on Day 8 of each period.
• a follow-up visit 5 - 9 days after the second period.
There are 4 treatments in this study: Treatment A, B, C, and D. The volunteer
will receive 2 of them: either A and B or C and D. Which treatments the
volunteer will receive, and the order in which he/she will receive them, will
be determined by chance. The study compound will be given as tablets or
capsules. One tablet contains 40 milligram PHA-022121 and one capsule contains
10 milligram PHA-022121.
Treatment Formulation Intake of* How often Day Dose per dosing Dose per day
A Extended release 1 tablet Once daily Day 1 to Day 5 40 milligram 40
milligram
B Immediate release 2 capsules Twice daily* Day 1 to Day 5 20 milligram 40
milligram
C Extended release 1 tablet Twice daily* Day 1 to Day 5 40 milligram 80
milligram
D Immediate release 4 capsules Twice daily* Day 1 to Day 5 40 milligram 80
milligram
* In case of twice daily dosing, this dosing will occur in the morning and
evening of Day 1 to Day 4 and a only a morning dose on Day 5. The doses will be
given 12 hours apart.
Intervention
There are 4 treatments in this study: Treatment A, B, C, and D. The volunteer
will receive 2 of them: either A and B or C and D. Which treatments the
volunteer will receive, and the order in which he/she will receive them, will
be determined by chance. The study compound will be given as tablets or
capsules. One tablet contains 40 milligram PHA-022121 and one capsule contains
10 milligram PHA-022121.
Treatment Formulation Intake of* How often Day Dose per dosing Dose per day
A Extended release 1 tablet Once daily Day 1 to Day 5 40 milligram 40
milligram
B Immediate release 2 capsules Twice daily* Day 1 to Day 5 20 milligram 40
milligram
C Extended release 1 tablet Twice daily* Day 1 to Day 5 40 milligram 80
milligram
D Immediate release 4 capsules Twice daily* Day 1 to Day 5 40 milligram 80
milligram
* In case of twice daily dosing, this dosing will occur in the morning and
evening of Day 1 to Day 4 and a only a morning dose on Day 5. The doses will be
given 12 hours apart.
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 of the puncture site. In some
individuals, a blood draw can sometimes cause pallor, nausea, sweating, low
heart rate, or drop in blood pressure with dizziness or fainting.
In total, we will take about 350 milliliters of blood from the volunteer from
screening to follow-up.
Heart tracing
To make a heart tracing, electrodeswill be placed on the arms, chest and legs.
Prolonged use of these electrodes can cause skin irritation.
Meals/Fasting
If the volunteer has 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 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.
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 sign an ICF indicating that the subject understands the purpose
of the study including the procedures required, potential risks involved, and
is willing to participate in the study before starting any screening activities.
2. Adult male or female subjects, between 18 to 65 years of age (inclusive) at
the time of informed consent.
3. Subject must have a body mass index (BMI) between 18.0 and 35.0 kg/m2
(inclusive), and a body weight not less than 50.0 kg, inclusive, at screening.
4. A subject may be enrolled if she/he is willing and able to adhere to the
contraceptive requirement as specified
5. All female subjects must have a negative serum β-human chorionic
gonadotropin (β-hCG) pregnancy test at screening and on Day -1 of each
treatment period.
6. Subject must be willing and able to adhere to the prohibitions and
restrictions as specified
7. Subject must be healthy on the basis of a medical evaluation that reveals
the absence of any clinically significant abnormality at screening per
Investigator discretion.
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 < 62mL/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 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 lower limit of normal range (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. Subject underwent surgery or has a medical condition that might
significantly affect absorption of medicines (e.g., stomach bypass,
cholecystectomy, etc.) as judged by the Investigator.
4. Subject has clinically significant abnormal values for hematology, clinical
chemistry or urinalysis at screening or at admission to the clinical site on
Day -1 as judged by the Investigator.
5. Subject, at screening, has a positive test for human immunodeficiency virus
(HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C
virus (HCV) antibodies.
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 | EUCTR2022-002683-77-NL |
| CCMO | NL82957.056.22 |