In this study, we will investigate how quickly and to what extent the new compound PTC857 is absorbed, metabolized, and eliminated from the body. Both unlabeled and radioactively labeled PTC857 will be administered. Unlabeled PTC857 will be given…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• To assess the rates and routes of excretion and calculate the mass balance of
total radioactivity(TRA) following a single oral dose of 250 mg
14C-PTC857 containing ~3.7 MBq (100 µCi) TRA, during repeated PTC857 dosing*.
• To assess the pharmacokinetics (PK) of TRA in whole blood and plasma
following a single oral dose of 250 mg 14C-PTC857 containing ~3.7 MBq (100 µCi)
TRA, during repeated PTC857 dosing*.
• To assess the metabolite profiles and the distribution of 14C-PTC857 and its
metabolite(s) in plasma, urine, and feces, following a single oral dose of 250
mg 14C-PTC857 containing ~3.7 MBq (100 µCi) TRA, during repeated PTC857 dosing*.
*6 days of oral dosing with 250 mg PTC857 BID before, and 7 days of oral dosing
with 250 mg PTC857 BID after the 14C-PTC857 dose.
Secondary outcome
• To assess the safety and tolerability of multiple oral doses of PTC857.
Background summary
PTC857 is a new compound that is being studied f or the treatment of
neurological diseases, such as amyotrophic lateral sclerosis (ALS). ALS is a
progressive nervous system disease that affects nerve cells in the brain and
spinal cord, causing loss of muscle control. There is currently no cure f or
this disease. Treatment is aimed at reducing the symptoms.
In neurological diseases, there is an overproduction of highly reactive
compounds that can damage cell structures, which can result in inf lammation in
the brain. PTC857 aims to reduce overproduction of the highly reactive
compounds by inhibiting a specific protein (15-lipoxygenase).
PTC857 has been given to humans bef ore in medical-scientific studies. PTC857
has also been studied extensively in the laboratory and in animals with higher
doses than those that will be given in this study. No major or clinically
relevant side effects were found.
In a previous clinical study (with 82 subjects), single PTC857 doses of 100 mg
to 1000 mg were administered and multiple doses of 250 mg twice daily, 500 mg
once daily, and 150 mg once or twice daily were administered for 14 days. In
another previous clinical study (with 16 subjects), 2 single doses of 150 mg
with 7 days between doses were administered. All these doses were overall well
tolerated and only mild side effects were reported.
Study objective
In this study, we will investigate how quickly and to what extent the new
compound PTC857 is absorbed, metabolized, and eliminated from the body. Both
unlabeled and radioactively labeled PTC857 will be administered. Unlabeled
PTC857 will be given multiple times to reach a steady exposure level.
Furthermore, we will investigate how safe PTC857 is and how well it is
tolerated when it is used by healthy subjects.
Study design
In total the volunteer will visit the research center 3 times:
• Once for the screening.
• Once for a stay in the research center. For the study, it is necessary that
the volunteer stays in the research center for at least 15 days (14 nights) and
at most 22 days (21 nights). Day 1 is thef irst day when the volunteer receives
the study compound. The volunteer is expected at the research center the day
before the day of first administration of the study compound, so on Day -1. The
volunteer will leave the research center at the latest on Day 21.
• Once for a follow-up visit.
Intervention
The volunteer will receive multiple doses of unlabeled PTC857 and a single dose
of 14C-labeled PTC857 as oral solutions using dosing syringes. The volunteer is
required to drink 240 mL water after each administration to rinse the mouth.
Below is an overview of the treatments:
Day 1 up to Day 6: PTC857 twice daily 250 mg
Day 7: 14C-PTC857 in the morning 250 mg 250 mg radioactively labeled PTC857
Day 7: PTC857 in the evening 250 mg
Day 8 up to Day 14: PTC857 twice daily* 250 mg
* The evening dose on Day 14 is not needed if it appears on Day 14 that the
volunteer has already reached the predetermined criteria.
On Day 7, after an overnight f ast, the volunteer will have to consume an
adapted breakfast within approximately 30 minutes prior to the 14C-PTC857 dose.
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 394 mL to 485 mL of blood from screening to
follow-up. This amount does not cause any problems in adults. To compare: a
blood donation involves 500 mL of blood being taken at once 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.
Fasting:
If someone 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 gagging. When the sample is taken from the back of the
nose, The volunteer may experience a stinging sensation and eyes may become
watery.
Corporate Court 100
South Plainfield 07080 NJ
US
Corporate Court 100
South Plainfield 07080 NJ
US
Listed location countries
Age
Inclusion criteria
1. Healthy male participants between 18 and 65 years of age, inclusive, at
Screening.
2. Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, and total body
weight >=50 kg, at Screening and Check-In.
3. Participants must understand the nature of the study and must provide a
signed and dated written informed consent before the conduct of any
study-related procedures.
4. Male participants sexually active with women of childbearing potential who
have not had a vasectomy must agree to use a barrier method of birth control
from check-In until 90 days after discharge. Males must also refrain from sperm
donations during this time period.
5. In good health, determined by no clinically significant findings from
medical history, physical examination, 12-lead electrocardiogram (ECG), vital
sign measurements, and clinical laboratory evaluations (congenital nonhemolytic
hyperbilirubinemia [eg, suspicion of Gilbert*s syndrome based on total and
direct bilirubin] is not acceptable) at Screening and/or Check-In as assessed
by the Investigator (or designee).
6. Willing and able to comply with the protocol.
7. History of on average 1 bowel movement per day (ie, no recent history of
constipation and/or irregular bowel movement).
Exclusion criteria
1. Significant history or clinical manifestation of any metabolic, allergic,
dermatologic, hepatic, renal, hematologic, pulmonary, cardiovascular,
gastrointestinal, neurological, respiratory, endocrine, or psychiatric
disorder, as determined by the Investigator (or designee).
2. History of significant hypersensitivity, intolerance, or allergy to sesame
oil, gelatin (bovine and/or porcine), titanium dioxide, or red iron oxide,
unless approved by the Investigator (or designee).
3. History of stomach or intestinal surgery or resection that would potentially
alter absorption and/or excretion of orally administered drugs (uncomplicated
appendectomy and hernia repair are allowed).
4. History of alcohol or drug/chemical abuse within 2 years prior to Screening,
or current evidence of substance dependence or self-reported alcoholic intake
>21 units per week. One unit of alcohol equals 360 mL beer, 45 mL liquor, or
150 mL wine.
5. Positive drug screen at Screening or Check-In or positive alcohol screen at
Check-In.
6. Use of tobacco- or nicotine-containing products within 1 month prior to
Check-In, or positive cotinine screen at Screening or Check-In. A positive
cotinine screen may be repeated once.
7. QT-interval corrected using Fridericia*s formula (QTcF) >=450 msec (based on
the mean of triplicate measurements taken at Screening).
Further criteria apply, see protocol.
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 | EUCTR2022-002302-25-NL |
| CCMO | NL82099.056.22 |