In this study, we will investigate how quickly and to what extent JDQ443 is absorbed, transported, and eliminated from the body. JDQ443 will be radioactively labeled with carbon-14 (14C). In this way, JDQ443 can be traced in blood, urine, feces, and…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To determine the rates and routes of excretion of total radioactivity
following a single 200 mg oral dose of [14C]JDQ443 in healthy male participants.
- To determine the PK of total radioactivity in whole blood and plasma
following a single 200 mg oral dose of [14C]JDQ443 in healthy male participants.
- To characterize the PK of JDQ443 and known key metabolites, if applicable, in
plasma and urine following a single 200 mg oral dose of [14C]JDQ443 in healthy
male participants.
Secondary outcome
- To assess the safety and tolerability of a single 200 mg oral dose of
[14C]JDQ443 in healthy male participants.
Background summary
JDQ443 is a new compound that may potentially be used for the treatment of
cancer. Mutations in a particular protein (the Kirsten rat sarcoma 2 viral
oncogene homolog [KRAS] G12C protein) promote cancer cell survival. KRAS G12C
mutations are found in approximately 30% of all human cancer types. To date,
there are not many approved therapies targeting mutations in the KRAS G12C
protein.
JDQ443 is a potent small molecule that can shift the KRAS G12C protein into an
inactive state. Preclinical studies show that JDQ443 has the potential to be a
promising therapy for patients with KRAS G12C mutant solid tumors.
Study objective
In this study, we will investigate how quickly and to what extent JDQ443 is
absorbed, transported, and eliminated from the body. JDQ443 will be
radioactively labeled with carbon-14 (14C). In this way, JDQ443 can be traced
in blood, urine, feces, and expired air.
We will also investigate how safe the new compound JDQ443 is and how well it is
tolerated when it is used by healthy participants.
We also investigate whether your genetic information has an effect on how your
body metabolizes JDQ443. 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
receives the study compound. The volunteer will leave the research center on
Day 22 of the study.
From Day 1 until Day 22, all urine and feces will be collected and blood and
expired air samples will be taken frequently to measure the amount of
radioactivity in the urine, feces, blood, and expired air. They should be aware
that if the radioactivity levels are still above predefined levels on Day 22,
they will need to return to the research center for up to 4 additional 24 hour
visits.
For the additional 24-hour visits, The volunteer is expected at the research
center at 11:00 h in the morning of Day 29, 36, 43, and 50. They will leave the
research center on Days 30, 37, 44, and 51, respectively. Each time they leave
the research center, they will be contacted by phone as soon as possible and be
told whether they have to come back for the next 24-hour visit or not.
During 24 hours prior to entry into the research center for the inhouse stay
and for the 24-hour visits, the volunteer will have to collect feces at home
and bring this to the research center.
Below is an overview of the days the volunteer stays at the research center, or
when they visit the research center.
- Screening
1 short visit between Day -28 and Day 2
- Arrival
Day -1
- Inhouse stay
Day -1 t/m Day 22
- Departure
Day 22
- 24-hour visits
Day 29 to Day 30*
Day 36 to Day 37*
Day 43 to Day 44*
Day 50 to Day 51*
- Follow-up
1 short visit 5 to 10 days after the last discharge
*Depending on the radioactivity levels in your bodily material, these visits
can be cancelled.
Intervention
The volunteer will once receive 200 milligram (mg) of 14C-labeled JDQ443 as a
small drink of 20 milliliters (mL). This amount contains 3.7 MBq (100 µCi)
radioactivity. After administration of the study compound, the vial will be
rinsed 4 times with approximately 30 mL of water, which they will also be
required to drink. Thereafter, they are required to drink an amount of
approximately 120 mL of water.
The volunteer will receive the study compound approximately 30 minutes after
the start of a standardized breakfast following an overnight fast (no food and
drinks except for water) of at least 10 hours.
Study burden and risks
Drawing blood may be painful or cause some bruising. On the day of
administration of the study compound, blood will be sampled very frequently
using an indwelling cannula to determine the course of the concentration of
JDQ443 in your blood over time. The use of the indwelling cannula can sometimes
lead to inflammation, swelling, hardening of the vein, blood clotting, and/or
bruising around the puncture site. In some individuals, a blood draw can
sometimes cause pallor, nausea, sweating, low heart rate, and/or a drop in
blood pressure with dizziness or fainting.
In total, we will take about 500 mL of blood between the screening and the
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. 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.
To make a heart tracing, electrodes will be placed on arms, chest, and legs.
Prolonged use of these electrodes can cause skin irritation.
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.
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, they may experience a stinging sensation and eyes may become watery.
Lichtstrasse 35 35
Basel 4056
CH
Lichtstrasse 35 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 60 years, inclusive, at screening.
3. In good health as determined by no clinically significant findings from
medical history,
physical examination, vital signs, 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:
- 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 45 to 90 beats per minute, inclusive.
5. Participants must weigh at least 50 kg and no more than 120 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 other investigational drugs within 6 months prior to admission (in
case of therapeutics with expected long half-lives such as immunoglobin G
antibodies) or use of other investigational drugs within 30 days prior to
dosing (for small-molecule drugs with daily dosing scheme), 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 PD or have an impact on participant
safety by the other investigational drug.
2. Evidence of any remaining PD effects not having yet returned to baseline
after previous exposure to an investigational drug (in the judgment of the
Investigator).
3. Contraindications or hypersensitivity to the investigational
compound/compound class or excipients being used in this study.
4. History or presence of malignancy of any organ system (other than localized
basal cell carcinoma of the skin or in-situ cervical cancer), treated or
untreated, within the past 5 years, regardless of whether there is evidence of
local recurrence or metastases.
5. Recent history (<3 months prior to screening) of nicotine product use or a
urine cotinine level >500 ng/mL at screening or baseline.
Further criteria apply, see protocol.
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 | EUCTR2021-006217-10-NL |
| CCMO | NL79956.056.21 |