The purpose of this study is to investigate how quickly and to what extent a new tablet formulation of CG-549 is absorbed and eliminated from the body. This information will be used to select a dose of CG-549 which is expected to be safe and…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PK:
- Plasma and urine CG-549 concentrations will be measured.
- The following plasma PK parameters will be estimated using noncompartmental
analysis from the plasma concentration-time data: Cmax, tmax, kel, t*, AUC0-t,
AUC0-inf, CL/F, and Vd/F.
- The following urine PK parameters will be estimated using noncompartmental
analysis from the urine concentration-time data: Aeurine and CLR.
Secondary outcome
Safety : Adverse events, clinical laboratory, vital signs, 12-lead
electrocardiogram, and physical examination.
Background summary
CG-549 is a new compound that may potentially be used for the treatment of
bacterial infections involving Staphylococcus aureus, including methicillin
resistant Staphylococcus aureus. CG-549 is an antibacterial drug that
obstructs a particular enzyme in the making of fatty acids. Since fatty acids
are part of the wall of bacterial cells, its making is critical for the
survival of bacteria. CG 549 is an antibiotic that only impacts bacteria that
rely on this particular enzyme (e.g., Staphylococcus aureus); it thus does not
impact other bacteria. This should allow preservation of the normal gut
microbiota as well as reduction of spread of antibiotic resistance across
multiple bacterial species.
Study objective
The purpose of this study is to investigate how quickly and to what extent a
new tablet formulation of CG-549 is absorbed and eliminated from the body. This
information will be used to select a dose of CG-549 which is expected to be
safe and potentially efficacious. It will also be investigated whether the
intake of food has an impact on the pharmacokinetics of CG-549. At last, it
will be investigated how safe the new compound CG-549 is and how well it is
tolerated when it is administered to healthy volunteers.
This study will be performed in 24 healthy male and female volunteers. The
study will be performed in 2 parts, Part A and Part B.
Study design
Part A:
The study will consist of 3 periods during which the volunteer will stay in the
research center for 5 days (4 nights). These periods will be separated by a
period of at least 2 weeks.
Day 1 of each period is the day of administration of the study compound. The
volunteers are expected at the research center at 2:00 PM in the afternoon
prior to the day of administration of the study compound, so on Day -1 of each
period. They will leave the research center on Day 4 of each period.
The volunteer will receive CG-549 three times as oral tablets with 240
milliliters of water. The volunteer will receive CG-549 after eating a high-fat
standardized breakfast. This breakfast must be started exactly on time and must
be finished within 20 minutes. The entire breakfast must be consumed. One of
the investigators will inspect the hands and mouth after the study compound
intake.
Part B:
The study will consist of 2 periods during which the volunteer will stay in the
research center for 5 days (4 nights). These periods will be separated by a
period of at least 2 weeks.
Day 1 of each period is the day of administration of the study compound. The
volunteers are expected at the research center at 2:00 PM in the afternoon
prior to the day of administration of the study compound, so on Day -1 of each
period. They will leave the research center on Day 4 of each period.
All volunteers will receive the study compound once with a breakfast and once
without a breakfast. The order in which this will occur will be determined by
chance. The breakfast will be high-fat or medium-fat and is standardized. The
breakfast must be eaten exactly on time (early in the morning) and within 20
minutes. The entire breakfast must be consumed. The 2 doses of CG-549 will be
given as oral tablets with 240 milliliters (mL) of water. One of the
investigators will inspect your hands and mouth after the study compound
intake. The amount of CG-549 that will be administered and whether the
breakfast will be high-fat or medium-fat (for a part of the subjects) will be
determined based on the results of Part A.
Intervention
Part A:
The volunteer will receive CG-549 three times as oral tablets with 240
milliliters of water. The volunteer will receive CG-549 after eating a high-fat
standardized breakfast. This breakfast must be started exactly on time and must
be finished within 20 minutes. The entire breakfast must be consumed. One of
the investigators will inspect the hands and mouth after the study compound
intake.
Part B:
All volunteers will receive the study compound once with a breakfast and once
without a breakfast. The order in which this will occur will be determined by
chance. The breakfast will be high-fat or medium-fat and is standardized. The
breakfast must be eaten exactly on time (early in the morning) and within 20
minutes. The entire breakfast must be consumed. The 2 doses of CG-549 will be
given as oral tablets with 240 milliliters (mL) of water. One of the
investigators will inspect your hands and mouth after the study compound
intake. The amount of CG-549 that will be administered and whether the
breakfast will be high-fat or medium-fat (for a part of the subjects) will be
determined based on the results of Part A.
Study burden and risks
CG-549 has been previously tested in the laboratory and on animals. The dose at
which no side effects were observed in rats was 100 mg per kilogram body weight
(mg/kg). Side effects that occurred at doses up to 400 mg/kg in rats resolved
within 2 days. The dose at which no side effects were observed in dogs was 400
mg/kg. Repeated dosing at an extremely high dose of 1000 mg/kg for 7 days in
dogs resulted in disturbances in the gastrointestinal tract. Overall, toxicity
studies with rats and dogs revealed no noteworthy findings.
CG-549 in capsule format has been administered to humans before in 3 studies.
In the first study, single-dose treatments of CG-549 at doses ranging from 80
to 1920 mg were considered safe and well tolerated in healthy male volunteers.
There were no side effects that were related to administration of CG-549.
In the second study, treatment with CG-549 once daily for 5 days at doses
ranging from 320 to 960 mg was considered safe and was well tolerated in
healthy male volunteers. However, 4 out of 6 volunteers who received CG 549
twice daily for 5 days at a dose of 640 mg had increased liver enzymes
(indicating liver toxicity) after they had left the research center. These
increased liver enzymes were related to administration of CG-549. All 4
volunteers recovered well without treatment. There were no other side effects
that were related to administration of CG-549.
In the third study, patients with bacterial skin infections due to
methicillin-resistant Staphylococcus aureus were treated with CG-549 once daily
for 10 to 14 days at a dose of 960 mg. The following side effects were observed
which were related to administration of CG 549: increased levels of enzymes
which are produced by the pancreas (amylase and lipase), headache, diarrhea,
nausea, vomiting, an increased heart rhythm, abnormal dreams, and flatulence.
Most side effects resolved well without treatment; only in 1 subject,
pancreatic enzymes were still elevated at the follow-up visit.
Taken together, the following side effects of CG-549 may occur: increased liver
enzymes, increased pancreatic enzymes, headache, diarrhea, nausea, vomiting, an
increased heart rhythm, abnormal dreams, and flatulence. The study compound may
also have side effects that are still unknown.
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising. On the days of administration of the study compound, blood
will be sampled frequently to determine the course of the concentration of
CG-549 in the blood over time.
In total, we will take about 260 mL of blood from you. 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 will be pasted at specific locations on
your arms, chest, and legs. Prolonged use of these electrodes can cause skin
irritation.
The high-fat breakfast is a big breakfast consisting of 2 fried eggs, fried
potatoes, and bacon among other things. The volunteer must consume the
breakfast entirely. Particularly for light eaters, it can be difficult to
consume the entire breakfast.
5F, Building A, Korea Bio Park 700 Daewangpangyoro, Bundanggu 700
Seongnamsi, Gyenoggido 13488
KP
5F, Building A, Korea Bio Park 700 Daewangpangyoro, Bundanggu 700
Seongnamsi, Gyenoggido 13488
KP
Listed location countries
Age
Inclusion criteria
1. Sex: male or female; females may be of childbearing potential or of
nonchildbearing potential (i.e., either surgically sterilized, physiologically
incapable of becoming pregnant, or at least 1 year postmenopausal [amenorrhea
duration of 12 consecutive months and a serum follicle stimulating hormone
(FSH) >33.4 IU/L]).
2. Age: 18 to 55 years, inclusive, at screening.
3. Body mass index (BMI): 18.0 to 30.0 kg/m2, inclusive, at screening.
4. Weight: >=50 kg at screening.
5. Status: healthy subjects.
Exclusion criteria
1. Previous participation in the current study.
2. Employee of PRA or the Sponsor.
3. History of bacterial or viral infection requiring treatment with antibiotics
or antivirals within 1 month prior to screening.
4. Presence or history of esophageal or gastroduodenal ulceration within 1
month prior to screening.
5. History of diseases or abnormalities of the liver or biliary system, other
than uncomplicated hepatitis A.
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 | EUCTR2019-003009-91-NL |
| CCMO | NL71288.056.19 |