A single-center, open-label study to investigate the absorption, distribution, metabolism and excretion (ADME) of INC280 after a single oral dose of 600 mg [14C] INC280 (5.55 MBq) in healthy male subjects

INC280 is a new investigational compound that may eventually be used for the
treatment of several forms of cancer. INC280 is a specific inhibitor of a
protein (the c-MET receptor tyrosine kinase) which plays an important role in
the development and progression of cancer. INC280 is not registered as a drug
but has been given to humans before.

The purpose of the study is to investigate how quickly and to what extent
INC280 is absorbed, distributed, metabolized (broken down) and eliminated from
the body (this is called pharmacokinetics). The compound to be administered
will be labeled with 14-Carbon (14C) and is thus radioactive (also called
radiolabeled).

The actual study will consist of 1 period during which the volunteer will stay
in the clinical research center in Zuidlaren for a minimum of 9 days (8 nights)
or 15 days (14 nights).

During the study the volunteer will receive the study medication after an
overnight fast (at least 10 hours) as 12 capsules of 50 mg each, together with
a minimum of 240 milliliters and a maximum of 480 milliliters of water.

Fasting will continue until 4 hours after administration of the study
medication. During fasting and after intake of the study medication, the
volunteers are allowed to drink water as they wish with the exception of 2
hours prior to until 2 hours after administration of study medication.

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

During the study teh volunteers will receive the study medication after an
overnight fast (at least 10 hours) as 12 capsules of 50 mg each, together with
a minimum of 240 milliliters and a maximum of 480 milliliters of water.

All potential drugs cause adverse events; the extent to which this occurs
differs.

INC280 is an investigational drug and not all of the side effects are known. In
previous clinical studies in healthy male subjects, a single dose of 600 mg
INC280 was found to be safe and well-tolerated resulting in only mild side
effects, which were primarily headache and nausea. Any possible long-term
effects of INC280 are also unknown.

We do not know the side effects of INC280 when given in combination with other
drugs. A combination of drugs might result in serious side effects. Some over
the-counter and prescription medications can reduce the effectiveness or
increase the side effects of INC280. Likewise, INC280 can increase the side
effects or lessen the effectiveness of some medications. This might result in
serious or even life-threatening side effects. You should always discuss the
use of any drugs (over- the-counter drugs, prescription, or illegal drugs or
health food supplements) with your doctor before taking INC280 and while you
are participating in this study.

In this study 14C-radiolabeled INC280 will be used. The amount of radioactivity
in this dose will be approximately 5.55 MBq (MBq = megaBecquerel, this is a
unit to express the amount of radioactivity in the study medication). The
average environmental background radiation burden in The Netherlands is
approximately 2 mSv per year (mSv = miliSievert, this is the unit which
indicates the burden on the human body; thus the effect on the human body of
the amount of radioactivity administered). The additional radiation burden in
this study due to the administration of approximately 5.55 MBq 14C labeled
INC280 is calculated to be 2.37 mSv. This is approximately 1.2 times the
average annual radiation burden.

Procedures: pain, minor bleeding, bruising, possible infection.