In this study we will investigate how safe the new compound leniolisib is and how well it is tolerated by healthy male participants.We also investigate how quickly and to what extent leniolisib is absorbed, transported, and eliminated from the body…
ID
Source
Brief title
Condition
- Immune system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the total recovery and relative excretion of radioactivity in
urine and feces after a single dose of 70 mg 14C-leniolisib, containing 40 µCi
of 14C-radioactivity administered as a solution for oral administration.
Secondary outcome
To determine the plasma PK parameters of total 14C-radioactivity and of
leniolisib;
To evaluate the safety profile of a single 70 mg dose of 14C-leniolisib.
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 investigate how safe the new compound leniolisib is and
how well it is tolerated by healthy male participants.
We also investigate how quickly and to what extent leniolisib is absorbed,
transported, and eliminated from the body. Leniolisib is radioactively labelled
with carbon-14 (14C). In this way leniolisib can be traced in blood, urine, and
feces.
Leniolisib has been investigated in humans before in previous drug studies. In
addition, it has been extensively tested in the laboratory and on animals.
Study design
For the study it is necessary that subjects stay in the research center for at
least 9 days (8 nights) and at most 13 days (12 nights). The length of their
stay depends on the amount of radioactivity that has left their body. From Day
8 onwards, the amount of radioactivity in their feces and urine is checked
daily. If the predetermined criteria have been reached, they will be informed
about this in the late afternoon and they may then leave the research center.
They will leave the research center on Day 12 the latest. If they do not yet
meet the set criteria then, 1 to 3 weekly 24-hour visits (1 night stay per 24
hour visit) will follow, until the radioactivity is low enough. These potential
visits will take place on Day 19/20, 26/27 and 33/34. There is also a follow-up
visit within 5 days after last visit. If the amount of radioactivity in blood
and urine on Day 8-12 is so low that it cannot be measured, then they only have
to collect a feces sample at home once weekly and bring it to the research
center on Day 19, 26, and 33.
Day 1 is the day when they receive the study compound. They will leave the
research center on Day 12 of the study.
During this study we will measure the amount of radioactivity left in blood,
urine, and feces. This means that we will take regular blood samples and that
we will collect all feces and urine from study compound intake until subjects
leave the research center. We will also ask them to collect a feces sample at
home from within 24 hours prior to entry in the research center.
If the radioactivity levels in feces and urine have not yet reached the
pre-defined criteria on Day 12, they will return to the research center for
24-hour visits for the collection of urine and feces on Day 19 and, if
applicable, also on Day 26 and 33. For the additional visits, they are expected
at the research center at 11:00h in the morning and they can leave after the 24
hours have passed (Day 20, 27, and 34). They will also be asked to collect
their feces at home within 24 hour prior to the start of these visits. They
will receive material for this.
During the 24-hour visit, their urine and feces will be collected, and blood
will be sampled to measure the amount of radioactivity. Depending on the test
results of the amount of radioactivity left in their blood, urine and feces,
remaining 24-hour visits can be cancelled. They will be contacted by phone as
soon as possible and be told if they have to come back for the additional
24-hour visits or not.
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
Stay - Arrival -> Day -1
Stay - In-house stay -> Day -1 till Day 8-12**
Stay - Departure -> Day 8-12**
24-hour visits* -> Day 19
24-hour visits* -> Day 26
24-hour visits* -> Day 33
Follow-up visit -> Within 5 days after last visit
* The 24 hour visits are only needed if subjects have not yet reached the
pre-defined criteria at the previous stay or visit.
** The length of the stay depends on the amount of radioactivity that has left
the body.
Subjects will be given leniolisib as an oral solution of 50 milliliters (mL).
After intake of the study compound, the vial will be rinsed three times with 50
mL of water, which they will also be required to drink.
Intervention
Subjects will receive 70 mg of 14C radioactively labeled leniolisib once (as an
oral solution of 50 milliliters (mL)).
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 390 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).
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. Subject has regular (daily) bowel movements;
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 formulation, 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. The radiation exposure from the previous 3 year period is over 10 mSv for
subjects who had been exposed to ionizing radiation above background as a
result of their work with radiation as Category A (classified) workers or as a
result of research studies they might have been involved in. Clinical
(therapeutic or diagnostic) exposure will not be included;
4. An occupation which requires monitoring for radiation exposure, nuclear
medicine procedures or excessive x-rays within the past 12 months;
5. History of clinically significant endocrine, gastrointestinal,
cardiovascular, haematological, hepatic, immunological, renal, respiratory,
neoplastic or genitourinary abnormalities or diseases;
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 | EUCTR2021-001807-33-NL |
| CCMO | NL78964.056.21 |