In this study we will investigate how safe the new compound INT-787 is and how well it is tolerated when it is used by healthy participants.We also investigate how quickly and to what extent multiple doses of INT-787 are absorbed, transported,…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part A:
To evaluate the safety and tolerability of single ascending doses of INT-787
capsule(s) administered orally to healthy male and female subjects
Part B:
To evaluate the safety and tolerability of multiple ascending doses of INT-787
capsule(s) administered orally for 14 days to healthy male subjects
Part C:
To assess the food effect on the PK of INT-787, and its tauro- and glyco-
conjugates (and other metabolites as applicable) following administration of a
single dose of INT-787 capsule(s) administered orally to healthy male subjects
Secondary outcome
Part A:
To evaluate the pharmacokinetics (PK) of INT-787, and its tauro- and
glycoconjugates (and other metabolites as applicable) following administration
of single ascending doses of INT-787 capsule(s) administered orally to healthy
subjects
To assess the gender effect on the PK of INT-787, and its tauro-and
glyco-conjugates (and other metabolites as applicable) following administration
of a single dose of INT-787 capsule(s) administered orally to healthy subjects.
To explore the possible relationships between dose, exposure, and FXR
activation biomarker responses as well as biomarkers of kidney function after
single ascending doses of INT-787.
Part B:
To evaluate the PK of INT-787, and its tauro- and glyco- conjugates (and other
metabolites as applicable) following administration of multiple ascending doses
of INT-787 capsule(s) administered orally to healthy male subjects
Part C:
To evaluate the safety and tolerability of a single dose of INT-787 capsule(s)
administered orally to healthy male subjects in fasted and fed conditions
Background summary
INT-787 is a new compound that may potentially be used for the treatment of
chronic (long lasting) liver diseases. Some of these diseases can be caused by
excessive alcohol consumption, but there may also be other causes. They are
often accompanied with inflammation of the liver. The inflammation leads to
damage and scar tissue (fibrosis) in the liver, which can lead to liver
cirrhosis, cancer, and eventually liver failure. INT-787 works by activating a
protein (FXR) that results, among other things, in a reduced inflammatory
response.
Study objective
In this study we will investigate how safe the new compound INT-787 is and how
well it is tolerated when it is used by healthy participants.
We also investigate how quickly and to what extent multiple doses of INT-787
are absorbed, transported, metabolized (broken down), and eliminated from the
body (this is called pharmacokinetics). Additionally, we will investigate if
and how INT 787 influences the composition and activity of the microbiota
(microorganisms) in the gastrointestinal tract. We will collect stool samples
for this.
We also look at the effect of your genetic information on your body*s response
to INT-787. This part of the study is optional.
We compare the effects of INT-787 with the effects of a placebo. A placebo is a
compound without any active ingredient (also called a *dummy pill*). Please
note that when the term *study compound* is used in this document, we mean
INT-787, placebo, or both.
INT-787 has not been used by humans before. It has been extensively tested in
the laboratory and on animals. INT-787 will be tested at various dose levels.
When Part B starts, INT-787 will have been administered to healthy participants
in Part A.
When Part C starts, INT-787 will have been administered to healthy participants
in Part A.
Study design
Part A:
For the research it is necessary to stay in the research center for 1 period of
6 days (5 nights). After this there is 1 short visit to the research center and
a follow-up check. The short visit is on Day 8 and the follow-up is on Day 15.
Day 1 is the day on which you receive the research drug. The volunteer is
expected on the day prior to administration of the study drug at the study
center. One must then report at approximately 2:00 pm. The research center is
left on Day 5 of the examination.
INT-787 or placebo is given as capsules by mouth with 240 milliliters (ml) of
water. Prior to administration, a fast is required for at least 10 hours and
the fast continues until 4 hours after administration. From 1 hour before to 1
hour after dosing, do not drink anything except the 240 mL of water that must
be taken with the dose.
Part B:
For the research it is necessary to stay in the research center for 1 period of
19 days (18 nights). After this there is 1 short visit to the research center
and a follow-up check. This short visit is on Day 21 and the follow-up is on
Day 28.
Day 1 is the first day on which the research drug is given. We expect
volunteers on the day prior to the first study drug administration at the study
center. They must then report at approximately 2 p.m. They leave the research
center on Day 18 of the examination. For the visits on Days 21 and 28 the
volunteer is expected to arrive at the research center at approximately 10:00
AM. INT-787 or placebo is given as capsules by mouth with 240 milliliters (ml)
of water. Whether the study drug is given after fasting or after eating will be
decided based on the results of Part C of this study. You may need to fast for
at least 10 hours before dosing.
Part C:
For the research it is necessary to stay in the research center for 2 periods
of 6 days (5 nights). In each period they also come for 1 short visit to the
research center. These short visit is on Day 8 of each period. There will be
approximately 4 weeks between doses, but this may change based on the results
of Part A of the study. The follow-up takes place between Day 15 of each
period. In both periods, Day 1 is the day on which the study drug is received.
We expect volunteers on the day prior to administration of the study drug at
the study center. One must then report at approximately 2:00 pm. The research
center is left on Day 5 of each period. For the visits on Days 8, 15 and 22,
you are expected to arrive at the research center at approximately 10:00 AM.
INT-787 is given as capsules by mouth with 240 milliliters (ml) of water. Prior
to administration, one must fast for at least 10 hours. All participants will
receive the study drug once with and once without breakfast. The order in which
this is done will be determined by drawing lots. Breakfast is a high-fat
breakfast with a fixed composition that must be started right on time and eaten
completely within 20 minutes. Eating is not allowed until 4 hours after taking
the study drug. From 1 hour before to 1 hour after dosing, you should not drink
anything except the drink that accompanies the high-fat breakfast and the 240
mL of water that must be taken with the dose
Intervention
Part A:
Group 1 Day 1 once INT-787 2.5 mg or placebo
Group 1 Day 1 once INT-787 5 mg or placebo
Group 3 Day 1 once INT-787 10 mg or placebo
Group 4 Day 1 once INT-787 25 mg or placebo
Group 5 Day 1 once INT-787 50 mg or placebo
Group 6 Day 1 once INT-787 100 mg or placebo
Group 7 Day 1 once INT-787 200 mg or placebo
Group 8 Day 1 once INT-787 300 mg or placebo
Group 9 Day 1 once INT-787 450 mg or placebo
Part B:
Group 1 day 1-14 INT-787 5 mg or placebo once daily
Group 2 day 1-14 INT-787 15 mg or placebo once daily
Group 3 day 1-14 INT-787 45 mg or placebo once daily
Group 4 days 1-14 INT-787 100 mg or placebo once daily
Group 5 days 1-14 INT-787 200 mg or placebo once daily
Part C:
INT-787 once per period, 2 times in total.
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, about 450 milliliters (mL) of blood is taken. This amount does not
cause any problems in adults.
Heart tracing
To make a heart tracing, electrodes will be placed on the arms, chest and legs.
To monitor the heart rate, electrodes will be placed at specific locations on
the chest and abdomen. Prolonged use of these electrodes can cause skin
irritation.
Meals/Fasting
If the volunteers 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 them 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.
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Age
Inclusion criteria
1. Subject must be male (18 to 55 years of age, inclusive) or female (gender
effect cohort only; 18 to 55 years of age, inclusive).
2. Female subjects (included in the gender effect cohort only) must be of
non-childbearing potential, who have undergone a sterilization procedure at
least 6 months prior to dosing with official documentation (e.g., hysteroscopic
sterilization, bilateral tubal ligation or bilateral salpingectomy,
hysterectomy, or bilateral
oophorectomy), or are postmenopausal with amenorrhea for at least 1 year prior
to dosing and folliclestimulating hormone (FSH) serum levels consistent with
postmenopausal status and serum pregnancy test at screening and upon admission
with a negative result as per Investigator*s judgment.
3.Male subjects who are sexually active with a woman of childbearing potential
and have not had a vasectomy must agree to use a barrier method of birth
control (e.g., either condom or partner with occlusive cap [diaphragm or
cervical/vault caps]). Male subjects must also agree to not donate sperm for
the duration
of the study and for at least 90 days after study discharge.
4. Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
5. Judged to be in good health on the basis of medical history, physical
examination, and routine laboratory measurements (i.e., without clinically
relevant pathology).
Exclusion criteria
1.History of any illness or condition that, in the opinion of the Investigator,
might confound the results of the study or pose an additional risk in
administering investigational product to the subjects.
2. Smokers (subjects who have smoked within 3 months of screening or those with
positive results from the cotinine urine test).
3. Inflammatory bowel disease, cholecystectomy or surgery of the
gastrointestinal tract that could interfere with pharmacokinetics of the study
medication (except appendectomy and simple hernia repair).
4. Routine treatment with prescription medications. Subjects should have
stopped taking any prescription and nonprescription medications at least 14
days before the first dosing of investigational product. Potential subjects
should only stop taking any prescription and nonprescription medications at the
direction of a
physician.
5. Consumption of herbal medications, dietary supplements, and specific fruit
products. Subjects should have stopped consumption of herbal medications or
dietary supplements (e.g., St. John*s Wort, ginkgo biloba, and garlic
supplements), vitamins, grapefruit, grapefruit hybrids or grapefruit juice,
Seville oranges,
pomelos, cranberries, pomegranates, star fruit, apples, vegetables from the
mustard green family (e.g., kale, broccoli, watercress, collard greens,
Brussels sprouts, and mustard) and charbroiled meats for 7 days prior to Day 1,
on any dosing day, and through the completion of the last PK sampling.1.
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 | EUCTR2021-001025-43-NL |
| CCMO | NL77625.056.21 |