A phase I study to investigate the pharmacokinetics, safety and tolerability of four different dosing regimens of GRC 17536 in healthy male volunteers using tablet formulation.

GRC 17536 is a new investigational compound that may eventually be used for the
treatment of acute and chronic pain conditions as well as respiratory
conditions such as asthma, chronic obstructive pulmonary disease (COPD), cough,
and related disorders. GRC 17536 is a molecule that specifically recognizes,
binds and blocks the function of the TRPA1 receptor. A receptor is a protein on
the surface of a cell to which a signaling molecule can bind, causing a change
in the activity of the cell. TRPA1 receptors are mainly present in neurons that
sense pain and play an important role in pain signaling and they are present in
nerves in the airways where it is thought to play an important role in
respiratory inflammation. The sensation of pain and inflammatory reactions can
be reduced by blocking the TRPA1 receptor.

GRC 17536 is not registered as a drug but has been given to humans before in 4
previous clinical studies .

n 2 out of 3 previous clinical studies a granule formulation (powder) of GRC
17536 was investigated and in 1 study various tablet formulations of GRC 17536
were investigated. The results from these studies showed that GRC 17536 is
absorbed better into the blood when administered as a tablet compared to
administration as a granule formulation. Therefore, the tablet formulations
have been selected for further investigation in this study.

The purpose of the study is to investigate how quickly and to what extent
multiple doses of the tablet formulations of GRC 17536 are absorbed and
eliminated from the body (this is called pharmacokinetics). From the obtained
data an optimal dose level for future studies in patients will be selected.
It will also be investigated to what extent multiple doses of the tablet
formulations of GRC 17536 are tolerated.

This study will be performed in 28 healthy male volunteers.

The actual study will consist of 1 period during which the volunteers will stay
in the clinical research center in Groningen for 29 days (28 nights).
They are expected at the clinical research center at 14:00 h in the afternoon
prior to the day of administration of study compound. They will be required not
to have consumed any food or drinks during the 4 hours prior to arrival in the
clinical research center (with the exception of water).
The volunteers will leave the clinical research center on Day 28.
The participation to the entire study, from pre-study screening until the post
study screening, will be maximally 63 days.

During the study the volunteers will receive GRC 17536 or placebo as oral
tablets with 240 milliliters of tap water after consumption of a meal.
On Day 1 and Day 21 they will have to fast until 4 hours after administration
of the morning dose. Then they will receive a lunch. During fasting and after
intake of the study compound, they are allowed to drink water, except from the
time of study drug administration until 1 hour after study drug administration
(apart from the water taken with the dose). In addition, the volunteers will
have to fast for 1 hour after the evening dose. For subjects receiving 360 mg
GRC 17536 or placebo, fasting restrictions as described above are also
applicable on Day 20.

One of the investigators will inspect the hands and mouth after study compound
intake.

n.a.

During the investigation, various assessements will be done that can be
experienced as more or less stressful.
Blood draw and the ECG can be experienced as stressful in this respect.