In this study we will investigate how safe the new compound VNRX-7145 and the combination of 2 study compounds, the new compound VNRX7145 and the approved compound ceftibuten, are and how well they are tolerated when they are used by healthy…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part 1
To evaluate the PK of VNRX 7145, its active metabolite VNRX5236 and ceftibuten
when a single dose of VNRX 7145 is co-administered with ceftibuten compared to
single doses of VNRX-7145 or ceftibuten administered alone.
Part 2
To evaluate the safety of repeated doses of 500 mg VNRX-7145 administered q8h
for 10 days in healthy adult volunteers.
Part 3
To evaluate the safety of multiple doses (10 days) of orally administered VNRX
7145 at 2 dose levels when co-administered with ceftibuten.
Secondary outcome
Part 1
To evaluate the safety of a single dose of VNRX-7145 co-administered with
ceftibuten compared to VNRX 7145 or ceftibuten administered alone.
Part 2
To evaluate the PK of VNRX-7145 and its active metabolite VNRX-5236 with
repeated doses (q8h for 10 days) of 500 mg VNRX-7145 in healthy adult
volunteers.
Part 3
To evaluate the PK of VNRX-7145, its active metabolite VNRX-5236, and
ceftibuten following multiple doses (10 days) of orally administered VNRX-7145
at 2 dose levels when co-administered with ceftibuten.
Background summary
The resistance of bacteria against antibiotics is an increasing problem in the
treatment of bacterial infections. A group of antibiotics, β-lactam
antibiotics, is less effective because bacteria develop an enzyme (β-lactamase)
that breaks down a central part of this group of antibiotics. VNRX-7145 is a
new compound that may potentially be used to improve the treatment of serious
bacterial infections. In the body, VNRX-7145 is converted to the active β-
lactamase inhibitor VNRX-5236.
Ceftibuten is an approved β-lactam antibiotic that is used to treat serious
bacterial infections (including inflammation in the lung, trachea, throat,
sinuses, middle ear, and bladder). The Sponsor is developing VNRX7145 to be
used in combination with ceftibuten.
Study objective
In this study we will investigate how safe the new compound VNRX-7145 and the
combination of 2 study compounds, the new compound VNRX7145 and the approved
compound ceftibuten, are and how well they are tolerated when they are used by
healthy participants.
We also investigate how quickly and to what extent VNRX-7145 and/or ceftibuten
are absorbed, transported, and eliminated from the body. In addition in part 2,
we look at the antibiotic effect of VNRX-7145 and ceftibuten in urine and
blood.
In part 1 we compare the effects of ceftibuten and VNRX-7145 alone with the
combination of ceftibuten and VNRX-7145.
In part 2 and 3 we compare the effects of ceftibuten in combination with
VNRX-7145 or placebo.
Ceftibuten is already being used in the treatment of serious bacterial
infections at a dose of 400 mg per day. The dose used in this study (in part 2
and 3) is higher (3 times 400 mg per day), but has been used by humans before.
VNRX-7145 has been used by humans before. In addition, it has been extensively
tested in the laboratory and on animals. In this study, VNRX-7145 will be
tested at 2 dose levels. The combination of VNRX-7145 and ceftibuten has not
been given to humans before.
Study design
The study will take a maximum of 7 weeks from the screening until the follow-up
visit. For the study it is necessary that subjects stay in the research center
for 1 period of 13 days (12 nights).
Part 1
Screening > Day -28 up to Day 2 prior to the first study drug administration
Arrival > Day -1
In-house stay > Day -1 up to Day 12
Departure > Day 12
Follow-up > Day 16 (±2 days)
Study compound administration on Day 1, Day 5 and Day 9. Subjects will be given
VNRX-7145 and ceftibuten, as oral capsules with 240 milliliters (mL) of (tap)
water. They will receive VNRX-7145 (Treatment 1A), ceftibuten (Treatment 1B),
and VNRX-7145 and ceftibuten (Treatment 1C). The sequence in which they will
receive the treatments will be decided by chance. One of the investigators will
inspect your hands and mouth after the study compound intake. This it to check
if you have taken the study compound.
Part 2 and 3
Screening > Day -28 up to Day 2 prior to the first study drug administration
Arrival > Day -1
In-house stay > Day -1 up to Day 12
Departure > Day 12
Follow-up > Day 17 (±2 days)
Part 2
Subjects will receive the following treatment 3 times daily (every 8 hours):
500 mg VNRX-7145 or placebo (Treatment 2). Which treatment they receive will be
determined by chance. Nine (9) participants will receive VNRX-7145 and 3
participants will receive placebo.
Part 3
Study compound administration on Day 1 to Day 10. Subjects will be given
VNRX-7145 or placebo and ceftibuten, as oral capsules with 240 milliliters (mL)
of (tap) water. They will receive one of the following treatments 3 times daily
(every 8 hours): 400 mg ceftibuten with 300 mg VNRX-7145 (Treatment 3A), 400 mg
ceftibuten with 500 mg VNRX-7145 (Treatment 3B), or ceftibuten placebo with
VNRX-7145 placebo (Treatment 3C) . Which treatment they receive will be
determined by chance. Ten (10) participants will receive Treatment 3A, 10
participants will receive Treatment 3B, and 4 participants will receive
Treatment 3C. One of the investigators will inspect your hands and mouth after
the study compound intake. This it to check if you have taken the study
compound.
Part 3 will only proceed after Part 2 is completed and the study compound was
well tolerated.
Intervention
Part 1
Treatment name | Treatment | How often
Treatment 1A | VNRX-7145 500 mg | once
Treatment 1B | Ceftibuten 400 mg | once
Treatment 1C | VNRX-7145 500 mg and Ceftibuten 400 mg | once
Part 2 and 3
Treatment name | Day | Treatment | How often
Treatment 2 | 1 to 9 | VNRX-7145 500 mg or VNRX-7145 Placebo | 3 times daily
Treatment 2 | 10 | VNRX-7145 500 mg or VNRX-7145 Placebo | once
Treatment 3A | 1 to 9 | VNRX-7145 300mg + Ceftibuten 400 mg | 3 times daily
Treatment 3A | 10 | VNRX-7145 300mg + Ceftibuten 400 mg | once
Treatment 3B | 1 to 9 | VNRX-7145 500mg + Ceftibuten 400 mg | 3 times daily
Treatment 3B | 10 | VNRX-7145 500mg + Ceftibuten 400 mg | once
Treatment 3C | 1 to 9 | VNRX-7145 Placebo + Ceftibuten Placebo | 3 times daily
Treatment 3C | 10 | VNRX-7145 Placebo + Ceftibuten Placebo | once
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,
sweating, low heart rate, or drop in blood pressure with dizziness or fainting.
In total, we will take about 500 mL of blood in part 1, 200 mL of blood in part
2 and 450 mL of blood in part 3. These amounts 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 will 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 subject 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.
74 East Swedesford Rd. Suite 100
Malvern PA 19355
US
74 East Swedesford Rd. Suite 100
Malvern PA 19355
US
Listed location countries
Age
Inclusion criteria
1. Willing to participate in the study, give written informed consent, and
comply with the study restrictions including lifestyle restriction outlined in
Section 6.4 of the protocol.
2. Healthy male and female .subjects between 18 and 55 years of age (inclusive).
3. Body mass index (BMI): >=18.5 kg/m2 and <=32.0 kg/m2, at Screening.
4. Normal blood pressure at Screening and Day -1, defined as a systolic value
greater than or equal to 90 mm Hg and less than or equal to 140 mm Hg and a
diastolic value less than 90 mm Hg. Values outside the range for inclusion may
be retested once if there is a clinical rationale for the out-of-range value.
5. Urine dipstick results for protein are negative or trace at Screening and
Day -1.
Exclusion criteria
1. Employee or family members of the clinical research organization (CRO), CRC,
or the Sponsor.
2. Female who is pregnant, lactating, or planning to attempt to become pregnant
during this study or within 90 days after dosing of study drug.
3. Male with a female partner who is pregnant or lactating or planning to
become pregnant within 90 days after the last dose of study drug administration.
4. Subject is participating in any other clinical study that involves the
administration of an investigational product at the time of screening or during
the course of the study or has received treatment with an investigational
product in the 30 days before Screening (90 days for an injectable biological
agent). See Protocol Section 7.6 Concomitant Treatment for more details.
5. Subject has a congenital or acquired immunodeficiency syndrome.
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 | EUCTR2021-001566-37-NL |
| CCMO | NL77461.056.21 |