In this study we will investigate how quickly and to what extent ganaplacide is absorbed, transported, and eliminated from the body. Ganaplacide will be radioactively labelled with carbon-14 (14C). In this way, ganaplacide can be traced in blood,…
ID
Source
Brief title
Condition
- Ectoparasitic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• To determine the routes and rates of excretion of [14C]ganaplacide related
radioactivity, including mass balance of total drug-related radioactivity in
urine, feces, and excretion of radioactivity via exhaled air, following a
single oral dose of [14C]ganaplacide in healthy male participants.
• To determine the PK of total radiolabeled components in blood and plasma
following a single 400 mg oral dose of [14C]ganaplacide in healthy male
participants.
• To characterize the PK of ganaplacide and known key metabolites M31 (RHF218)
and M37a (GOU089), if applicable, in plasma following a single 400 mg oral dose
of [14C]ganaplacide in healthy male participants.
Secondary outcome
• To assess the safety and tolerability of a single 400 mg oral dose of
[14C]ganaplacide in healthy male participants.
Background summary
Ganaplacide is a new compound that may potentially be used for the treatment of
malaria. The most important symptoms of malaria are fever, headache, and muscle
pain.
Malaria is a disease caused by parasites (small organisms that can only
reproduce at the expense of a plant, animal, or human). These parasites can
enter the body during a mosquito bite.
Ganaplacide has shown activity against several forms of the malaria parasite.
It does this by inhibiting various processes in the parasite*s cell.
Study objective
In this study we will investigate how quickly and to what extent ganaplacide is
absorbed, transported, and eliminated from the body. Ganaplacide will be
radioactively labelled with carbon-14 (14C). In this way, ganaplacide can be
traced in blood, urine, feces, and exhaled air.
We will also investigate how safe the new compound ganaplacide is and how well
it is tolerated when it is used by healthy participants.
Further we will also investigate whether genetic information has an effect on
how the body metabolizes ganaplacide. This part of the study is not
mandatory.
Study design
For the study, it is necessary that the volunteer stays in the research center
for 1 period of 23 days (22 nights). Day 1 is the day that the volunteer will
receive the study compound. The volunteer is expected at the research center
the day before the day of intake of the study compound, so on Day -1. The
volunteer will leave the research center on Day 22 of the study.
From Day 1 until Day 22, all urine and feces of the volunteer will be collected
and blood and exhaled air samples will be taken frequently to measure the
amount of radioactivity in the urine, feces, blood, and exhaled air. If the
radioactivity levels are still above predefined levels on Day 22, the volunteer
will need to return to the research center for up to 7 additional 24-hour
visits.
During 24 hours prior to entry into the research center for the inhouse stay
and for the 24-hour visits, the volunteer has to collect feces at home and
bring this to the research center.
Intervention
You will once receive 400 milligram (mg) of 14C-labeled ganaplacide as 4
capsules with 240 milliliters (mL) of water.
These capsules have to be swallowed within 3 to 5 minutes. These 4 capsules
contain 3.7 MBq (100 µCi) radioactivity
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 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 600 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 at once 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 may 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.
Fasting:
If someone 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 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 gagging. When the sample is taken from the back of the
nose, The volunteer may experience a stinging sensation and eyes may become
watery.
Lichtstrasse 35
Basel 4056
CH
Lichtstrasse 35
Basel 4056
CH
Listed location countries
Age
Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study.
2. Healthy males, aged 18 to 55 years, inclusive, at screening.
3. In good health as determined by no clinically significant findings from
medical history, physical examination, vital signs, electrocardiogram (ECG),
and laboratory tests at screening.
4. At screening and at baseline (Day -1), vital signs after 5 minutes in supine
position must be within the following ranges (unless deemed not clinically
significant by the investigator; the clinical considerations must be
documented):
• Body temperature from 35.0°C to 37.5°C, inclusive.
• Systolic blood pressure (BP) from 90 to 139 mmHg, inclusive.
• Diastolic BP from 45 to 89 mmHg, inclusive.
• Pulse rate from 40 to 90 beats per minute, inclusive.
5. Participants must weigh at least 50 kg to participate in the study and must
have a body mass index (BMI) within the range of 18.0 to 29.9 kg/m² at
screening. BMI=body weight (kg)/height2 (m2).
6. Participants agree to be available for the entire duration of the study and
to be able to adhere to the study restrictions and visit schedule.
7. Participants must be able to communicate well with the investigator and to
comply with the requirements of the entire study.
Exclusion criteria
1. Use of another investigational drug within the following time intervals
before dosing:
• For investigational drugs with long half-life (e.g., antibodies): use of
another investigational agent at screening, or 6 months prior to dosing, or
within a period corresponding to less than 5 half-lives of the agent before
dosing, whichever is longer; or longer if required by local regulations.
• For investigational drugs with short half-life (e.g., small molecules): use
of another investigational drug at screening, or 30 days prior to dosing, or
within a period corresponding to less than 5 half-lives of the drug before
dosing, whichever is longer; or longer if required by local regulations.
The investigator is expected to apply the appropriate due diligence
(considering available information in public, IBs, and/or patient information)
to ensure that the washout times detailed above are sufficient to avoid a
carry-over of PK or pharmacodynamics (PD) or have an impact on participant
safety by the other investigational drug.
2. History of hypersensitivity to the investigational compound/compound class
or excipients being used in this study.
3. History or presence of malignancy of any organ system, treated or untreated,
within the past 5 years, regardless of whether there is evidence of local
recurrence or metastases.
4. Recent history (<3 months prior to screening) of nicotine product use or a
urine cotinine level >500 ng/mL at screening or baseline.
5. Use of any prescription drugs (including moderate and strong CYP3A
inhibitors or inducers), over-the-counter (OTC) medications, herbal
supplements, or cannabis/marijuana/cannabidiol-containing products, within 4
weeks prior to dosing. Note: If needed (i.e. an incidental and limited need up
to 2 g per day), acetaminophen is acceptable, but must be documented in the
concomitant medications page of the eCRF.
6. Use of any dietary supplements (vitamins included) within 2 weeks prior to
dosing.
7. Significant illness which has not resolved within 2 weeks prior to dosing.
Further criteria apply, see protocol.
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 | EUCTR2022-001090-30-NL |
| CCMO | NL81529.056.22 |