In this study we will compare leniolisib as capsules with leniolisib as tablets. We compare this in terms of how quickly and to what extent each form of leniolisib is absorbed, transported, and eliminated from the body (this is called…
ID
Source
Brief title
Condition
- Immune system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine if 70 mg of leniolisib administered as a single dose of the hard
gelatin capsule (HGC) formulation is bioequivalent (within 0.80-1.25 as the
bioequivalence boundaries) to 70 mg of leniolisib administered as a single
70-mg film-coated tablet (FCT).
Secondary outcome
To evaluate the tolerability of leniolisib after both doses.
Background summary
Leniolisib is a new compound that may potentially be used for the treatment of
Activated Phosphoinositide 3-kinase Delta Syndrome (APDS). APDS is a disorder
that impairs the immune system. Individuals with this condition often have low
levels of white blood cells, which normally recognize and attack foreign
invaders, such as viruses and bacteria, to prevent an infection. Beginning in
childhood, people with APDS develop recurrent infections, particularly in the
lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can
lead to a condition called bronchiectasis, which damages the passages leading
from the windpipe to the lungs (bronchi) and can cause breathing problems. APDS
affects approximately 1-2 per million persons globally and there is currently
no approved treatment available. Leniolisib works by inhibiting a specific
protein that is not functioning normally and believed to be the cause of the
progression of this disease.
Study objective
In this study we will compare leniolisib as capsules with leniolisib as
tablets. We compare this in terms of how quickly and to what extent each form
of leniolisib is absorbed, transported, and eliminated from the body (this is
called pharmacokinetics). We will also compare how safe each form of leniolisib
is and how well they are tolerated when they are given to healthy participants.
Leniolisib has been used by humans before in previous drug studies. In
addition, it has been extensively tested in the laboratory and on animals.
Study design
The study will take a maximum of 7 weeks from the screening until the follow-up.
Stay in the research center for 2 periods of 6 days (5 nights). Day 1 of each
period is the day when subjects receive the study compound. They will leave the
research center on Day 5 of each period.
Below is an overview of the days they stay at the research center, or when they
visit the research center.
Screening -> Day -28 till -2
Period 1 and 2 - Arrival -> Day -1
Period 1 and 2 - In-house stay -> Day -1 until Day 5
Period 1 and 2 - Departure -> Day 5
Follow-up -> Day 5 of Period 2
Subjects will be given leniolisib once as an oral capsule in one period and
once as an oral tablet in the other period. In both periods, leniolisib will be
given together with 240 milliliters of water after fasting overnight for at
least 10 hours. Fasting will continue until 4 hours after the dose, and
drinking water is not allowed during these 4 hours.
The order in which they will receive the different leniolisib forms will be
determined by chance. There are two possible sequences. Please refer to the
table below:
Sequence 1 -> Period 1: Tablet, Period 2: Capsule
Sequence 2 -> Period 1: Capsule, Period 2: Tablet
One of the investigators will inspect hands and mouth after the study compound
intake. This it to check if they have taken the study compound.
There will be at least 7 days between the intakes of the study compound.
Intervention
Subjects will receive leniolisib twice: once as a capsule and once as a tablet.
Each dose of leniolisib will be 70 milligram.
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 about 240 milliliters (mL) of blood. 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 (rash and itching).
Fasting
If you 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, they may experience a stinging sensation and the eyes may become
watery.
10 Independance Blvd. 4th Floor
Warren NJ 07059
US
10 Independance Blvd. 4th Floor
Warren NJ 07059
US
Listed location countries
Age
Inclusion criteria
1. Male between 18 and 45 years of age (both inclusive) at the screening visit;
2. Subject has Dutch or English as native language;
3. Body mass index between 18.5 and 30.0 kg/m2 (both inclusive);
4. Subject is judged to be in good health based on medical history, physical
examination, vital sign measurements, and laboratory safety tests performed at
the screening visit and prior to administration of the initial dose of study
drug;
5. Subjects, if not surgically sterilized, must agree to use at least 1 form of
contraception and not donate sperm from first admission to the clinical
research center until after the follow-up. For this study, contraception for
the male subject (and his female partner) is defined as using hormonal
contraceptives, an intrauterine device, a diaphragm, a cervical cap, or a
condom. Total abstinence, in accordance with the lifestyle of the subject, is
also acceptable;
Exclusion criteria
1. Employee of PRA or the Sponsor;
2. History of known sensitivity or intolerability to leniolisib or to any
related compound or excipients in the formulations, or history of significant
multiple and/or severe allergies (including latex allergy) or has had an
anaphylactic reaction or significant intolerability to prescription or
non-prescription drugs or food;
3. History of clinically significant endocrine, gastrointestinal,
cardiovascular, haematological, hepatic, immunological, renal, respiratory,
neoplastic or genitourinary abnormalities or diseases;
4. Subject has a history of any illness that, in the opinion of the study
investigator, might confound the results of the study or poses an additional
risk to the subject by their participation in the study;
5. Positive polymerase chain reaction (PCR) test for SARS-CoV-2 at admission or
within 8 weeks prior to screening or check-in, or contact with COVID-19
positive (or suspected) persons within 14 days prior to dosing;
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 | EUCTR2021-001791-42-NL |
| CCMO | NL78449.056.21 |