REC-3964 is a new investigational drug, meaning that it has not yet been approved or marketed in the Netherlands or anywhere else at this time.In this study, REC-3964 is investigated in humans for the first time. REC-3964 has not been used by humans…
ID
Source
Brief title
Condition
- Other condition
- Bacterial infectious disorders
Synonym
Health condition
Clostridium difficile
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the safety and tolerability of single ascending doses (SAD) and
multiple ascending doses (MAD) of REC-3964 administered orally to healthy
subjects.
Secondary outcome
Secondary Objectives:
• To characterize the pharmacokinetics (PK) of REC-3964 and its enantiomer,
REC-3974, in plasma and urine following single and multiple oral doses of
REC-3964 in healthy subjects.
Exploratory Objectives:
• To investigate the metabolite profile of REC-3964 in plasma following single
and multiple oral doses of REC-3964 in healthy subjects.
• To investigate the potential genetic variants influencing the PK of REC-3964
in healthy subjects.
• To investigate potential blood biomarkers of REC-3964 activity following
single and multiple oral doses in healthy subjects.
• To evaluate changes in cytochrome P450 (CYP)3A activity following multiple
oral doses of REC-3964 in healthy subjects.
• To estimate the fraction of unbound REC-3964 in plasma following single oral
doses of REC-3964 in healthy subjects.
Background summary
REC-3964 is a new compound that may potentially be used for the treatment of
Clostridium difficile infections. An infection with this bacterium is known to
cause the release of toxins in the gut leading to stomach pain (abdominal pain)
and watery diarrhea. Severe infections can occur when normal gut bacteria are
disrupted and can lead to hospitalization or even death. REC-3964 is found to
have a suppressing effect on these toxins and protects cells in the gut in this
manner. Contrary to antibiotics, REC-3964 is found to not alter normal bacteria
in the gut. REC 3964 may potentially be used for the treatment of (acute)
severe cases of Clostridium difficile infections.
Study objective
REC-3964 is a new investigational drug, meaning that it has not yet been
approved or marketed in the Netherlands or anywhere else at this time.
In this study, REC-3964 is investigated in humans for the first time. REC-3964
has not been used by humans before. It has been extensively tested in the
laboratory and on animals.
The purpose of this study is to test the safety and tolerability of REC-3964
when it is taken by healthy subjects.
In this study, we will also investigate how quickly and to what extent REC-3964
is absorbed, transported, and eliminated from the body.
The study will also include collecting a blood sample for genotyping to look at
the effect of your genetic information on your body*s response to REC-3964.
Study design
Part A
Screening -> Day -28 up to Day -2
Treatment period - Arrival -> Day -2
Treatment period - In-house stay -> Day -2 up to Day 3
Treatment period - Departure -> Day 3
Follow-up -> Between Day 6 and Day 8
Part B
Screening -> Day -28 up to Day -2
Treatment period - Arrival -> Day -2
Treatment period - In-house stay -> Day -2 up to Day 16
Treatment period - Departure -> Day 16
Follow-up -> Between Day 18 and Day 22
Intervention
Part A
Starting dose 50 mg REC-3964 or placebo orally once on D1 (doses in subsequent
groups to be determined).
Part B
Starting dose to be determined REC-3964 or placebo orally from D1 to D14: One
time, two times (every 12 hours) or three times (every 8 hours) each day
Study burden and risks
Blood draw
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula (a tube in a vein in the arm) 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 102 (Part A) or 199 (Part B) milliliters (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 each
time. If the investigator thinks it is necessary for the safety of a subject,
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 (small, plastic patches) will be placed on
arms, chest and legs. To monitor the electrical activity of the heart over a
longer period, electrodes (small, plastic patches) will be placed on the chest
and abdomen. Prolonged use of these electrodes can cause skin irritation (rash
and itching).
Meals
Standardized meals will be given.
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 subjects 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.
S Rio Grande St. 41
Salt Lake City UT 84101
US
S Rio Grande St. 41
Salt Lake City UT 84101
US
Listed location countries
Age
Inclusion criteria
1. Subject is male or female aged >= 18 to <= 65 years. For Cohort A6 and
potentially for Cohort B5, subject is male or female aged > 65 years (note:
there is no upper limit for the subject*s age).
2. Subject must provide written informed consent prior to initiation of any
study procedures.
3. Subject*s body mass index is between 18 and 32 kg/m2, inclusive, with a
minimum body weight of 50 kg.
4. Subject is healthy as determined by medical history, physical examination,
vital signs, and 12 lead ECG. For any abnormalities, the subject may be
included only if the Investigator judges the abnormalities or deviations from
normal to be not clinically significant.
5. Subject*s clinical laboratory test results (hematology including
reticulocyte count, biochemistry, coagulation, urinalysis, comprehensive
metabolic panel, and complete blood count) are clinically acceptable as
determined by the Investigator at Screening and Admission.
Exclusion criteria
1. Subject has any clinically significant laboratory abnormality or illness
which, in the opinion of the Investigator, could interfere with the conduct or
interpretation of the study or put the subject at risk.
2. Subject has any condition that, in the opinion of the Investigator, could
affect drug absorption (eg, stomach or intestinal surgery such as
cholecystectomy or bariatric surgery, gastroesophageal reflux disease,
irritable bowel syndrome, or celiac disease).
3. Subject has a known history of hypersensitivity to the drug class or its
excipients.
4. Subject has a history of alcohol or substance abuse within 1 year prior to
screening for study participation, or is currently using alcohol, drugs of
abuse, or any prescribed or over-the-counter medication in a manner, which, in
the opinion of the Investigator, indicates abuse.
5. Subject has been treated with prescription, over-the-counter, dietary, or
herbal supplements that are CYP3A inhibitors or inducers within 14 days before
the first dose of study drug: eg, ketoconazole, itraconazole, voriconazole,
posaconazole, clarithromycin, telithromycin, nefazodone, rifampin, rifapentine,
rifabutin, grapefruit juice, Valencia oranges, or St. John*s Wort.
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 | EUCTR2022-002403-38-NL |
| CCMO | NL81881.056.22 |