In this study we will investigate how quickly and to what extent BTZ-043 is absorbed, transported, metabolized, and eliminated from the body (this is called pharmacokinetics). BTZ-043 is radioactively labelled with carbon-14 (14C). In this way BTZ-…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Tuberculosis
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To determine the rates and routes of excretion of [14C]BTZ-043-related
radioactivity, including mass balance of total drug-related radioactivity in
urine and feces (and vomit, if applicable), following the oral administration
of a single 500 mg dose of [14C]BTZ-043 in healthy male volunteers.
- To determine the PK of total radioactivity in whole blood and in plasma.
- To characterize the plasma PK of BTZ-043 and main metabolites by liquid
chromatography-mass spectrometry (LC-MS), if applicable.
- To characterize the urine concentrations of BTZ-043 and main metabolites by
LC-MS, if applicable.
Secondary outcome
- To assess the safety and tolerability of a single 500 mg oral dose of BTZ-043
administered to healthy male volunteers.
Background summary
BTZ-043 is a new compound that may potentially be used for the treatment of
tuberculosis. Tuberculosis is the most deadly infectious disease in the world
that generally affects the lungs and is usually caused by the Mycobacterium
tuberculosis bacteria. New compounds are urgently needed to combat
multidrug-resistant Mycobacterium tuberculosis (which is not responding to some
compounds anymore), which remains a serious public-health challenge.
Study objective
In this study we will investigate how quickly and to what extent BTZ-043 is
absorbed, transported, metabolized, and eliminated from the body (this is
called pharmacokinetics). BTZ-043 is radioactively labelled with carbon-14
(14C). In this way BTZ-043 can be traced in blood, urine, and feces.
We will also investigate how safe the new compound BTZ-043 is and how well it
is tolerated when it is used by healthy participants.
Study design
The study will take a maximum of 8 weeks from the screening until the follow-up
visit.
For the study it is necessary that the volunteer stays in the research center
for one period of at least 6 days (5 nights). If necessary, this period can be
prolonged to a maximum of 9 days (8 nights).
The volunteer can leave after the 24-hour collection interval on Day 12 and Day
16. There is a follow-up visit on Day 31.
The volunteer will receive a single dose of 500 mg 14C-labeled radioactive
BTZ-043.
Intervention
The volunteer will receive a single dose of 500 mg 14C-labeled radioactive
BTZ-043.
The volunteer will be given BTZ-043 as a cloudy drink (suspension) of 100
milliliters (mL). After administration of the study compound, the vial will be
rinsed twice with 70 mL of water, which the volunteer is also be required to
drink. Thereafter the volunteer is also required to drink an additional amount
of 140 mL (tap) water.
The volunteer may be given a standardized or a high-fat breakfast after an
overnight fast (no eating or drinking) of at least 10 hours. Thereafter, the
volunteer will be given the study compound. The volunteer may also receive the
study compound without receiving a breakfast. Fasting continues for another 4
hours after dosing. Water is allowed during fasting, except from 1 hour prior
to dosing until 1 hour after dosing.
During the first 4 hours after administration of the study compound the
volunteer is not be allowed to lie down (with the exception of medical
procedures that require lying down), as this may influence the uptake of the
study compound.
Study burden and risks
Possible side effects:
The study compound may cause side effects.
BTZ-043 has already been studied in 24 healthy persons and 24 patients with
tuberculosis. The following side effects are often observed (in 1 in 10 people
or more):
• Dizziness
• Headache
• Hypertension (high blood pressure)
• Nausea
• Hyperhidrosis (increased sweating)
• Abdominal pain
The study compound may also have (serious) side effects that are still unknown.
In addition to unknown side effects, there is a (small) chance that an allergic
reaction will occur. This can be caused by the study compound or other
ingredients that are used to prepare the formulation.
Possible discomforts:
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 450 milliliters (mL) of blood from the volunteer.
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 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 (small, plastic patches) will be placed at
specific locations on the volunteers arms, chest and legs. Prolonged use of
these electrodes can cause skin irritation (rash and itching).
Meals
The volunteer may receive a high-fast breakfast before the administration of
the study compound. The high-fat breakfast is a big breakfast containing eg, 2
fried eggs, fried potatoes and bacon or brie (see Appendix C for the full
composition). The volunteer must consume the whole breakfast within 20 minutes.
It can be difficult to consume the entire breakfast, particularly for light
eaters.
Fasting
If the volunteer has 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 volunters
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 volunteers throat may cause him to gag. When the sample is
taken from the back of the volunteers nose, he may experience a stinging
sensation and his eyes may become watery.
Marchioninistr. 15
Munich 81377
DE
Marchioninistr. 15
Munich 81377
DE
Listed location countries
Age
Inclusion criteria
1. Sex : male
2. Age : 18 years to 55 years, inclusive, at screening.
3. Body mass index (BMI) : 18.0 to 29.0 kg/m2, inclusive, at screening.
4. Weight : 55 to 90 kg, inclusive, at screening.
5. Status : healthy subjects.
6. Male subjects, if not surgically sterilized, must agree to use adequate
contraception and not donate sperm from admission to the clinical research
center until 90 days after the follow-up visit. Adequate contraception for the
male subject (and his female partner, if she is of childbearing potential) is
defined as using hormonal contraceptives or an intrauterine device combined
with at least 1 of the following forms of contraception: a diaphragm, a
cervical cap, or a condom. Total abstinence, in accordance with the lifestyle
of the subject, is also acceptable.
7. All prescribed medication must have been stopped at least 30 days prior to
admission to the clinical research center.
8. All over-the-counter medications, vitamin preparations (especially vitamin
C), other food supplements, and herbal medications (eg, St. John*s wort) must
have been stopped at least 14 days prior to admission to the clinical research
center. An exception is made for paracetamol, which is allowed up to 48 hours
prior to study drug administration.
9. No vaccination within 14 days prior to study drug administration.
10. Ability and willingness to abstain from alcohol from 48 hours (2 days)
prior to screening and admission to the clinical research center.
11. Ability and willingness to abstain from methylxanthine-containing beverages
or food (coffee, tea, cola, chocolate, and energy drinks), grapefruit (juice),
corn (whole corn kernels and popcorn), cruciferous vegetables, and bitter
oranges from 48 hours (2 days) prior to admission to the clinical research
center.
12. Good physical and mental health on the basis of medical history, physical
examination, clinical laboratory, ECG, and vital signs, as judged by the
Investigator.
13. Willing and able to sign the ICF.
Exclusion criteria
1. Participation in another study with a radiation burden of >0.1 mSv and <=1
mSv in the period of 1 year prior to screening; a radiation burden of >1.1
mSv and <=2 mSv in the period of 2 years prior to screening; a radiation burden
of >2.1 mSv and <=3 mSv in the period of 3 years prior to screening, etc.
2. Exposure to radiation for diagnostic reasons (except dental X-rays and plain
X-rays of thorax and bony skeleton [excluding spinal column]), or during work
within 1 year prior to drug administration.
3. Irregular defecation pattern (less than once per day on average).
4. Employee of PRA, Nuvisan, or the Sponsor.
5. History of relevant drug and/or food allergies.
6. Using tobacco products within 60 days prior to drug administration.
7. History of alcohol abuse or drug addiction (including soft drugs like
cannabis products).
8. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines
[including ecstasy], cannabinoids, barbiturates, benzodiazepines,
gamma-hydroxybutyric acid, tricyclic antidepressants, and alcohol) at screening
or admission to the clinical research center.
9. Average intake of more than 24 grams of alcohol per day.
10. Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus
(HCV) antibodies, or HIV 1 and 2 antibodies.
11. Participation in a drug study within 30 days prior to drug administration
in the current study. Participation in more than 4 drug studies in the 12
months prior to drug administration in the current study.
12. Donation or loss of more than 450 mL of blood within 60 days prior to drug
administration. Donation or loss of more than 1.5 liters of blood in the 10
months prior to drug administration in the current study.
13. Significant and/or acute illness within 5 days prior to drug administration
that may impact safety assessments, in the opinion of the Investigator.
14. Unwillingness to consume the Food and Drug Administration (FDA)-recommended
high-fat breakfast.
15. Unsuitable veins for infusion or blood sampling.
16. Positive nasopharyngeal PCR test for SARS-CoV-2 on Day -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 | EUCTR2021-000449-42-NL |
| ClinicalTrials.gov | NCT04874948 |
| CCMO | NL77661.056.21 |