- To evaluate the relative bioavailability between the new eltrombopag capsule formulation (CPS) and the marketed tablet formulation (FCT) at single oral doses of 25 mg and 75 mg, in healthy subjects in the fasted state.- To evaluate the PK…
ID
Source
Brief title
Condition
- Platelet disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- AUClast, AUCinf, Cmax
Tmax, Tlag, T1/2, CL/F, Vz/F
Secondary outcome
Incidence of adverse events (AEs) and severe adverse events (SAEs), changes in
vital signs, changes in electrocardiograms (ECGs), changes in laboratory
results (hematology, blood chemistry, and coagulation panel).
Background summary
The purpose of Part 1 is to investigate how the new capsule formulation of
eltrombopag functions in comparison to the reference marketed film-coated
tablets of eltrombopag in healthy volunteers.
Eltrombopag is not a new compound; it is already available in the market as a
tablet under various dosages.
It will be investigated how quickly and to what extent eltrombopag new capsules
are absorbed and eliminated from the body compared to eltrombopag marketed
tablets (this is called pharmacokinetics).
The safety of eltrombopag as an oral capsule will also be compared to the
safety of eltrombopag as an oral tablet.
Eltrombopag is a compound which is on the market for the treatment of
thrombocytopenia. Thrombocytopenia is a condition in which platelet levels in
blood are abnormally low. Platelets are tiny blood cells that form clots to
stop bleeding. Thrombocytopenia can be caused by various diseases such as
chronic immune thrombocytopenia (ITP), severe aplastic anemia (SAA) and chronic
hepatitis Ccaused thrombocytopenia.
Thrombocytopenia may not give any symptoms and is sometimes picked up with a
blood test. Some individuals with thrombocytopenia may experience external
bleeding. Examples of external bleeding are nosebleeds and/or bleeding gums.
Eltrombopag is currently on the market as a tablet. Novartis has now developed
a capsule formulation of eltrombopag. This capsule formulation might overcome
certain shortcoming that is related to the tablet. This shortcoming includes
interference with the absorption of eltrombopag due to certain kind of foods.
When the tablet formulation is given along with food with high calcium content,
the absorption of eltrombopag by the intestine is decreased. The new capsule
formulation is designed to overcome this shortcoming observed with the tablet
formulation.
The new capsule has been tested in the laboratory. The test indicated that
absorption of the capsule is better than the absorption of the tablet, also
when given in combination with different kind of foods.
The purpose of Part 3 is to investigate what the effect of food and calcium is
on how quickly and to what extent eltrombopag is absorbed and eliminated from
the body (this is called pharmacokinetics). It will be evaluated how the
pharmacokinetics of eltrombopag (capsule formulation) are affected if it is
given under 4 different conditions: after fasting, after eating a
low-fat/low-calorie breakfast, and after eating a high-fat/high-calorie
breakfast with high or low calcium.
Furthermore, it will be investigated how safe eltrombopag is and how well it is
tolerated when it is administered to healthy volunteers.
Eltrombopag is not a new compound; it is already available in the market as a
tablet under various dosages.
Study objective
- To evaluate the relative bioavailability between the new eltrombopag capsule
formulation (CPS) and the marketed tablet formulation (FCT) at single oral
doses of 25 mg and 75 mg, in healthy subjects in the fasted state.
- To evaluate the PK comparability between the new eltrombopag CPS at the
dose(s) adjusted for relative bioavailability and eltrombopag FCT at 75 mg,
after single oral dose of each, in healthy subjects in the fasted state.
- To evaluate the impact of high-fat-high-calorie and low-fat-low-calorie
meals, low or high in calcium content, on the rate and extent of absorption of
eltrombopag CPS.
To evaluate the safety and tolerability of single oral doses of eltrombopag
administered as CPS and FCT in healthy subjects under fasted conditions (Parts
1 and 2), and after high-fat-high-calorie or low-fat-low-calorie meals, low or
high in calcium content, vs. fasted dosing conditions (Part 3)
Study design
The study consists of 4 periods during which the subject will stay for a
minimum of 3 days (2 nights) and a maximum of 7 days (6 nights) per period. If
the subject choose to stay for 3 days, you will have to come back to the
research facility for short visits on the 4 subsequent days (Day 3 to Day 6).
For these short visits you have to be at the research center at 10:00 h in the
morning. There will be a period of 7 to 10 days without any visits between
dosing in each period.
30 days after the last period or after the last visit of the last period, or
from the day of early discontinuation, you will receive a phone call. This
follow-up phone call will consist of questions about your wellbeing.
The volunteers will be tested for the presence of coronavirus upon admission to
the research center. Until the test results are available, they will be
separated from other volunteers in a separate room, and only have very limited
contact with study staff. This is to avoid virus spread from potentially
infected volunteers to other volunteers or to the study staff. Until the
results are available, it is not known whether they are infected and can
potentially infect others. The test results will be available within one hour.
If the volunteer test positive for coronavirus, they cannot participate in the
study.
Intervention
The study will consist of 4 periods. In total the subject will receive one
single dose of 25 mg and 75 mg eltrombopag as an oral capsule, and 25 mg and 75
mg eltrombopag as an oral tablet (1 single dose per period), each single dose
being separated from each other by 7 to 10 days. Every time eltrombopag will be
given with 240 milliliters (mL) of (tap) water. The order in which they subject
will receive eltrombopag in the different doses and formulations will be
determined by chance.
Study burden and risks
Eltrombopag may cause side effects.
The following side effects are most frequently observed (in 1 in 10 people or
more):
• common cold
• feeling sick
• diarrhea
• cough
The study compound may also have side effects that are still unknown. In
addition to unknown side effect, there is a (small) chance that an allergic
reaction will occur. This can be caused by the study compound or the excipients.
Drawing blood and/or insertion of the indwelling cannula (tube in an arm vein)
may be painful or cause some bruising.
In total, we will take about 300 milliliters (mL) of blood from the subject.
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 (small, plastic patches) will be pasted at
specific locations on your arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).
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
the throat may cause the volunteer 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.
ParkLake Avenue, Suite 400 4130
Raleigh 27612
US
ParkLake Avenue, Suite 400 4130
Raleigh 27612
US
Listed location countries
Age
Inclusion criteria
- Male and female subjects who are 18 to 55 years of age on the day of Informed
Consent signature
- Subjects in good health condition as determined by no clinically significant
findings from medical history, physical examination, vital signs, and ECG, as
well as laboratory values within the reference range at the local laboratory,
unless deemed not clinically significant by the Investigator or designee
- Body mass index (BMI) of 18.0 to 29.9 kg/m2, with body weight greater than or
equal to 50 kg for males and 45 kg for females and no more than 120 kg
Exclusion criteria
- A history or presence of clinically significant ECG abnormalities or a family
history or presence of prolonged QT-interval syndrome
- Presence of hepatitis B or C virus, or human immunodeficiency virus
- Clinical evidence of renal disease or liver disease or liver injury
- Any surgical or medical condition which might significantly alter the
absorption, distribution, metabolism or excretion of drugs, such as
gastrectomy, gastroenterosomy, bowel restriction or colecystectomy
- Administration of CYP3A4/5 inhibitors or inducers within 4 weeks prior to
screening and until 2 weeks after EOT, for their potential interaction with
hormonal contraceptive methods
- Consumption of any antacids, e.g., liquid antacids (e.g., Maalox, Mylanta,
Amphogel, Milk of Magnesia), chewable antacids (e.g., TUMS*) during 14 days
prior the first dose of study medication and until end-of-treatment
-Not willing to avoid the following fruits and their juices: grapefruit,
grapefruit hybrids, Seville oranges, pomelos, pomegranates, cranberries and
star fruits from 14 days prior to the first dosing and until the
end-of-treatment
- Use of any prescription or non-prescription medication (OTC) (including
aspirin and non-steroidal anti-inflammatory drugs [NSAIDs]), herbal medication,
dietary supplements or vitamins during 14 days prior to first dosing and until
end-of-treatment
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 | EUCTR2019-004674-26-NL |
| CCMO | NL72617.056.20 |