In this study we will investigate the influence of a high-calorie, high-fat meal on the uptake, breakdown, and elimination of the study compound PHA-022121. We will also investigate how safe PHA-022121 is and how well it is tolerated when it is used…
ID
Source
Brief title
Condition
- Haematological disorders NEC
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the influence of a high-calorie, high-fat (HCHF) meal on the
single-dose pharmacokinetics of a 40 mg extended-release (XR) PHA-022121 oral
formulation and its metabolites (e.g. M2-D)
Secondary outcome
To evaluate the safety and tolerability of a 40 mg XR formulation of PHA-022121
administered as a single oral dose in the absence and presence of a HCHF meal.
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, 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.
To study the effect of food, the study compound will be given once after
fasting and once after a high-calorie, high-fat meal. The result of this
research can be used to make recommendations in the future on how best to use
the compound.
Study objective
In this study we will investigate the influence of a high-calorie, high-fat
meal on the uptake, breakdown, and elimination of the study compound
PHA-022121.
We will also investigate how safe 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 8 completed drug studies
and 206 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.
• 2 times for stays in the research center of 4 days (3 nights) each.
Day 1 of each period is the day when the study compound is administered and the
volunteer will leave the research center on Day 3 of each period.
• a follow-up visit 5 - 9 days after the last period.
Intervention
PHA-022121 will be given 1 time per period, so 2 times in total. Each dose that
the volunteer will receive is 40 milligrams.
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, sweating, low heart rate, or drop in blood
pressure with dizziness or fainting.
In total, we will take about 250 milliliters (mL) of blood from the volunteer
from screening to follow-up. This amount does not cause any problems in adults.
If the investigator thinks it is necessary for the safety of a subject, 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 the arms, chest and legs.
Prolonged use of these electrodes can cause skin irritation.
Meals/Fasting
The high-fat, high-calorie breakfast is a big breakfast containing eg, 2 fried
eggs, fried potatoes and bacon. The volunteer must consume the whole breakfast
within 20 minutes or less. It can be difficult to consume the entire breakfast,
particularly for light eaters.
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.
5. All female subjects must have a negative serum β-human chorionic
gonadotropin (β-hCG) pregnancy test at Screening and at Day -1 of each
treatment period.
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 < 62 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 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.
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 | EUCTR2022-002728-11-NL |
| CCMO | NL82642.056.22 |