A randomized, double-blind, placebo-controlled study of the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of CFTX-1554 in healthy subjects, with comparison of intake of CFTX-1554 as liquid formulation and as capsule, and after a high-fat breakfast versus fasted.

CFTX-1554 is a new compound that may potentially be used for the treatment of
nerve pain (peripheral neuropathic pain). Neuropathic (nerve) pain is a chronic
condition caused by nerve damage, which can result from conditions like
diabetes and herpes infection. Current treatments have limited effectiveness
and significant side effects. CFTX-1554 is a new potential treatment for this
condition, which acts in a different way from the current treatments by
blocking a different pain pathway called the AT2 receptor.

In this study we will investigate how safe the new compound CFTX-1554 is and
how well it is tolerated when it is used by healthy participants.

We also investigate how quickly and to what extent CFTX-1554 is absorbed,
distributed, metabolized, and eliminated from the body. In addition, we look at
the effect of CFTX-1554 on the body.

CFTX-1554 has not been used by humans before. It has been extensively tested in
the laboratory and on animals. CFTX-1554 will be tested at various dose levels.

We will compare the effects of CFTX-1554 with the effects of a placebo.

For this study we are looking for 107 healthy male or female participants. The
study will consist of 3 parts, Part A, Part B and Part C.

Part A:
The study will take a maximum of 5 weeks from the screening until the follow-up
visit.
For the study it is necessary that the volunteer stays in the research center
for 1 period of 4 days (3 nights).
Between Day 8 and Day 13 the volunteers health will be checked for the last
time. The appointment for this follow up visit will be made during the study.

Part A (Group A5 only):
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 a maximum of 4 periods of 4 days (3 nights)
Between Day 8 and Day 13 of the fourth period the volunteers health will be
checked for the last time. The appointment for this follow up visit will be
made during the study.

Part B:
The study will take a maximum of 7 weeks from the screening until the follow-up
visit.
For the study it is necessary that the volunteer stays in the research center
for 1 period of 17 days (16 nights).
Between Day 21 and Day 26 the volunteers health will be checked for the last
time. The appointment for this follow up visit will be made during the study.

Part C:
The study will take a maximum of 9 weeks from the screening until the follow-up
visit.
For the study it is necessary that the volunteer stays in the research center
for 4 periods of 4 days (3 nights).
Between Day 8 and Day 13 of the fourth period the volunteers health will be
checked for the last time. The appointment for this follow up visit will be
made during the study.

Part A:
The planned dose levels for the study are as follows:
Group Day Treatment* How often
A1 1 CFTX-1554 30 mg* (3 participants) or placebo (2 participants) once
A2 1 CFTX-1554 90 mg* (3 participants) or placebo (2 participants) once
A3 1 CFTX-1554 250 mg* (6 participants) or placebo (2 participants) once
A4 1 CFTX-1554 500 mg* (6 participants) or placebo (2 participants) once
A5 1 CFTX-1554 1000 mg* (6 participants) or placebo (2 participants) once
A6 1 CFTX-1554 1500 mg* (6 participants) or placebo (2 participants) once
A7 1 CFTX-1554 2000 mg* (6 participants) or placebo (2 participants) once

* In case the dose level will be lower or higher than planned, the volunteer
will be informed verbally.

Part A (Group A5 only):
The planned dose levels for the study are as follows:
Group Day Treatment How often Formulation Food status
A6 1 A: CFTX-1554 1000 mg (6 participants) or placebo (2 participants) once
Liquid Fasted
1 B: CFTX-1554 1000 mg (6 participants) once Liquid High-fat breakfast
1 C: CFTX-1554 1000 mg (6 participants) once Capsule Fasted
1 D: CFTX-1554 1000 mg (6 participants) once Capsule High-fat breakfast

Part B:
The planned dose levels for the study are as follows:
Group Day Treatment How often
B1 1-14 CFTX-1554 xx mg* (8 participants) or placebo (2 participants) once
daily or twice daily for 14 days
B2 1-14 CFTX-1554 xx mg* (8 participants) or placebo (2 participants) once
daily or twice daily for 14 days
B3 1-14 CFTX-1554 xx mg* (8 participants) or placebo (2 participants) once
daily or twice daily for 14 days
B4 1-14 CFTX-1554 xx mg* (8 participants) or placebo (2 participants) once
daily or twice daily for 14 days

* The doses are not known yet and will be based on the results of Part A. The
volunteer will be informed verbally which dose the volunteer will receive.


Part C:
Group C1 has 4 periodes. On day 1 of each period a single dose of xx CFTX-1554
will be administered.
* The doses are not known yet and will be based on the results of Part A. The
volunteer will be informed verbally which dose the volunteer will receive.

Possible side effects:
The study compound may cause side effects.

As CFTX-1554 will be administered to humans for the first time in this study,
side effects of CFTX-1554 in humans are not known yet. CFTX-1554 has been
studied extensively in the laboratory and in animals. A 28-day study in rats
showed mild enlargement of liver cells and a 28-day study in dogs showed
salivation, vomiting, diarrhea and an increase in blood pressure. These side
effects mainly occurred at the highest doses. These side effects also stopped
after the administration of the study compound was stopped.

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.

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, seating, low heart rate, or drop in blood
pressure with dizziness or fainting.

In total, we will take about (Part A) 99 (Part A, Group A5 only) 342 (Group B)
292 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 may be more than the
amount indicated above.

Heart tracing
To make a heart tracing, electrodes (small, plastic patches) will be placed on
the volunteers arms, chest and legs. To monitor your heart rate, electrodes
(small, plastic patches) will be placed on the chest and abdomen. Prolonged use
of these electrodes can cause skin irritation (rash and itching).

Fasting/Meals (Part A, Group A5 only)
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. The
high-fat breakfast is a big breakfast containing eg, 2 fried eggs, fried
potatoes and bacon. The volunteer must consume the whole breakfast within 20
minutes. It can be difficult to consume the entire breakfast, particularly for
light eaters.

Questionnaires:
We will ask the volunteer to complete a questionnaire about sleepiness, a
questionnaire about alertness, calmness and contentment, and a questionnaire
about potential effects of the study compound.

Coronavirus test
Samples for the coronavirus test will be taken from the back of the volunteers
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 the volunteer to gag. When the
sample is taken from the back of the volunteers nose, the volunteer may
experience a stinging sensation and the volunteers eyes may become watery.