The purpose of this study is to investigate how safe ceftibuten is and how well it is tolerated when it is administered at higher dose levels than those currently available on the market (daily doses up to 400 mg). It will also be investigated how…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the safety of increasing doses of oral ceftibuten (at and beyond
the currently approved dose level) in healthy adult volunteers. Safety will be
evaluated by the collection of adverse events (AEs), vital signs, clinical
laboratory data, electrocardiograms (ECGs), and physical examinations.
Secondary outcome
To evaluate the pharmacokinetics (PK) of increasing doses of ceftibuten (cis-
and trans-) following single and multiple doses in healthy adult volunteers as
measured by plasma and urine drug concentrations.
Background summary
Ceftibuten is an approved antibiotic that is used to treat serious bacterial
infections (including inflammation in the lung, trachea, throat, sinuses,
middle ear, and bladder). However, some bacteria are resistant against this
type of antibiotics. Therefore, the Sponsor is developing a new compound
(VNRX-7145), to be used in combination with ceftibuten. When ceftibuten is used
in combination with VNRX-7145, the doses of ceftibuten will be higher than the
doses that are currently available on the market (daily doses up to 400 mg). In
this study, VNRX-7145 will not be administered to any of the volunteers.
Although ceftibuten is an approved antibiotic, some of the doses that will be
investigated in this study are not approved.
Study objective
The purpose of this study is to investigate how safe ceftibuten is and how well
it is tolerated when it is administered at higher dose levels than those
currently available on the market (daily doses up to 400 mg). It will also be
investigated how quickly and to what extent ceftibuten is absorbed and
eliminated from the body (this is called pharmacokinetics).
The effects higher doses of ceftibuten on the electrical activity (conduction)
of the heart are not known. Therefore, these effects will be investigated by
continuous monitoring of the heart rhythm (Holter monitoring).
The effects of ceftibuten will be compared to the effects of a placebo. A
placebo is a medicine without any active ingredient.
This study will be performed in 36 healthy male or female volunteers. The study
will consist of up to 3 groups of 12 volunteers each.
Study design
Ceftibuten will be given as oral capsules with 240 milliliters (mL) of water.
Whether subjects will receive ceftibuten or placebo will be determined by
chance. Per group, 9 volunteers will receive ceftibuten and 3 volunteers will
receive placebo. Neither the subject, nor the responsible doctor knows if
ceftibuten or placebo will be administered. However, if it is important for the
subjects health, for example in case of a serious side effect, this information
can be looked up during the study.
Please refer to the table in the protocol to see the planned dose levels for
each group. The dose of ceftibuten that will be administered in Group 1 is
equal to the dose that is currently available on the market. Group 1 serves as
control for the doses to be administered in Groups 2 and 3. Doses to be
administered to Groups 2 and 3 are not currently approved for marketing. The
dose in Group 3 will only be administered if the lower dose in Group 2 was
found to be well tolerated according to the safety committee that monitors the
study, and in case of no objection by the Medical Research Ethics Committee.
The study will be discontinued if, in the opinion of the investigators,
unacceptable side effects appear.
The actual study will consist of 1 period during which the subjects will stay
in the research center for 14 days (13 nights). Day 1 is the first day of
administration of the study compound. Subjects are expected at the research
center at 14:00 h in the afternoon prior to the day of first administration of
the study compound. They will leave the research center on Day 13 of the study
and return for a follow up visit between Day 19 and 21.
Upon admission to the research center, it will be tested if the volunteer is a
carrier of the coronavirus. Until the test results are available, they will be
separated from other volunteers and only have very limited contact with study
staff. This is to avoid virus spread from potentially infected volunteers to
other volunteers or to the study staff. Until the results are available, it is
not certain whether they are infected or not and if they can thus potentially
infect others. The test results will be available within a few hours. If the
volunteer tests positive for coronavirus, they cannot participate in the study.
Intervention
Ceftibuten will be given as oral capsules with 240 milliliters (mL) of water.
Whether subjects will receive ceftibuten or placebo will be determined by
chance. Per group, 9 volunteers will receive ceftibuten and 3 volunteers will
receive placebo. Neither the subject, nor the responsible doctor knows if
ceftibuten or placebo will be administered. However, if it is important for the
subjects health, for example in case of a serious side effect, this information
can be looked up during the study.
Please refer to the table in the protocol to see the planned dose levels for
each group. The dose of ceftibuten that will be administered in Group 1 is
equal to the dose that is currently available on the market. Group 1 serves as
control for the doses to be administered in Groups 2 and 3. Doses to be
administered to Groups 2 and 3 are not currently approved for marketing. The
dose in Group 3 will only be administered if the lower dose in Group 2 was
found to be well tolerated according to the safety committee that monitors the
study, and in case of no objection by the Medical Research Ethics Committee.
The study will be discontinued if, in the opinion of the investigators,
unacceptable side effects appear.
Study burden and risks
Ceftibuten is available on the market since 1995 at a dose of 400 mg per day.
Ceftibuten is well tolerated at once daily doses of 400 mg or greater. The side
effects are primarily related to the gastrointestinal system and usually
resolve over time. The following side effects are most frequently observed (in
1 [1%] out of 100 people or more):
• nausea (4%)
• headache (3%)
• diarrhea (3%)
• dyspepsia (disturbance in the digestive system) (2%)
• dizziness (1%)
• abdominal pain (1%)
• vomiting (1%)
All drugs, including antibiotics like ceftibuten, can have side effects,
including an allergic reaction, which can occur and be severe and/or
life-threatening, and may require emergency care. All antibiotics, including
ceftibuten, carry a risk of developing an infection with a bacteria called
Clostridium difficile. The severity of such an infection can range from mild
diarrhea to a life-threatening large bowel infection. In addition, the use of
antibiotics could promote the growth of other bacteria and fungus.
Changes in laboratory tests related to liver function, blood clotting, and
counts of blood cells can occur with ceftibuten. In healthy adult volunteers,
single doses of up to 2 grams of ceftibuten did not result in abnormal
laboratory tests. As part of this clinical trial, laboratory tests related to
liver function, blood clotting, and counts of blood cells will be monitored.
The study compound may also have side effects that are still unknown.
Many side effects go away when treatment is stopped, but in some cases, it is
possible that the side effects could be serious, long lasting, permanent, or
life threatening. If subjects have a side effect during this study, the
responsible doctor will explain to them what possible treatment options there
are to make side effects less serious and what risks may be associated with
these treatments.
Possible discomforts due to procedures:
Drawing blood and/or insertion of the indwelling cannule may be painful and/or
cause some bruising.
To make a heart tracing, electrodes will be pasted at specific locations on the
arms, chest and legs. To monitor the heart rate, electrodes will be pasted at
specific locations on the chest and abdomen. Prolonged use of these electrodes
can cause skin irritation.
A sample for the coronavirus test will be taken from the back of the nose and
throat using a swab. Taking the sample 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 the volunteer 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.
E. Swedesford Road, Suite 100 74
Malvern PA 19355
US
E. Swedesford Road, Suite 100 74
Malvern PA 19355
US
Listed location countries
Age
Inclusion criteria
1. Willing to participate in the trial, give written informed consent, and
comply with the trial restrictions.
2. Gender: male or female; females may be of childbearing potential (using
highly effective contraception) with a negative serum pregnancy test, or of
nonchildbearing potential, at screening and Day 1.
3. Age: 18 to 55 years, inclusive, at screening.
4. Body mass index (BMI): >=18.5 kg/m2 and <= 30.0 kg/m2.
5. Normal blood pressure, defined as a systolic value greater than or equal to
90 mm Hg and less than 140 mm Hg and a diastolic value greater than or equal to
45 mm Hg and less than 90 mm Hg (screening and Day -1).
Further criteria apply
Exclusion criteria
1. Employee of the CRO, CRC, or the Sponsor.
2. Female (or male with a partner) who is pregnant, lactating, or planning to
attempt to become pregnant during this study or within 90 days after the last
administration of study drug.
3. Use of any investigational drug or device within 30 days prior to screening
(90 days for an injectable biological agent). Participation in more than 4
other drug studies in the 12 months prior to the first drug administration in
the current study.
4. Congenital or acquired immunodeficiency syndrome.
5. History or presence of current cardiovascular, respiratory, hepatic, renal,
gastrointestinal, endocrine, autoimmune, hematologic, neoplastic, or neurologic
disorders or any other disease that, in the opinion of the Investigator, poses
an unacceptable risk to the subject.
Further criteria apply
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 | EUCTR2019-003745-15-NL |
| CCMO | NL72729.056.20 |