A single-center, open-label study to investigate the absorption, distribution, metabolism and excretion (ADME) of LEE011 after a single oral dose of 600 mg [14C]LEE011 (0.37 MBq) in healthy male subjects

LEE011 is a new investigational compound that may eventually be used for the
treatment of advanced cancers. LEE011 is a specific inhibitor of protein
complexes (the cyclin-dependent kinase enzyme complexes) which play an
important role in the development and progression of cancer. LEE011 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
LEE011 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 you will stay in the
clinical research center in Zuidlaren for 23 days (22 nights). After this
period it is possible that you may have to come back for a maximum of 4
additional visits during which you will stay in the clinical research center in
Zuidlaren for 2 days (1 night).

During the study the volunteers will receive the study medication after an
overnight fast (at least 10 hours) as 3 capsules of 200 mg each, together with
approximately 250 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.

During the first 4 hours after study medication intake the volunteers will have
to rest in an upright seated position. The volunteers will not be allowed to
lie down, except when indicated as such by one of the investigators, as this
may influence the uptake of the drug.

The volunteer will receive a single dose of 600 mg radiolabeled study
medication in the form of 3 capsules of 200 mg each

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

LEE011 is an investigational drug and not all of the side effects are known.
Serious side effects, including death, are a possibility. The long-term effects
of LEE011 are also unknown. Risks are possible side effects of study medicine
given alone or in combination with other medication(s), and those related to
any of the study procedures (e.g. taking blood, biopsy, and imaging scans).

Based on the data from ongoing studies in cancer patients who received multiple
doses of LEE011 alone or in combination with other medications, the following
are the possible risks with taking LEE011.

Most frequent side effects of LEE011 (> 20% incidence):
* Low white blood cell count which can increase the risk for infections
* Low red blood cell count which can lead to tiredness and weakness
* Low platelets count which can lead to easy bruising and bleeding.
* Nausea and/or vomiting
* Diarrhea
* Tiredness or fatigue

Frequent side effects of LEE011 (10 to 20% incidence):
* Changes in electrical activity of the heart called QTc prolongation. This is
an abnormality of the heart rhythm and may cause dizziness,
palpitations, fainting and in severe cases loss of consciousness and
death
* Mouth sores, or pain, inflammation and/or infection of the of the mouth and
throat
* Increase in creatinine (a waste product) and a decrease in the kidneys*
ability to handle the body*s waste
* Decrease in appetite

Less frequent side effects of LEE011 (5-9% incidence):
* Low levels of protein in the blood
* High blood sugar
* Skin rash
* General aches including headache, stomach ache, back ache, or joint pain
* Fever
* Nosebleeds
* Dizziness

Infrequent but important side effects of LEE011 (<5% incidence):
* Low levels of sodium in the blood
* Low levels of calcium in the blood
* High levels of potassium in the blood
* High blood pressure
* Blockage in the blood vessels of the lung usually caused by blood clot(s)
* High blood levels of liver enzymes and bilirubin (yellow pigment found in
bile which is made by the liver) and possible liver damage
* Potential accumulation of LEE011 in the thyroid gland. In rats, LEE011 was
found to accumulate in the thyroid gland but there was no
evidence of damage to the thyroid gland. There have been no reports of
abnormal thyroid function in any patient so far.
* One patient participating in a trial (CMEK162X2114) combining LEE011 with
MEK162 (another investigational drug) died from bleeding in
the brain. The treating physician considered the fatal brain bleed to
be related to the combination of MEK162 and LEE011.

We do not know the side effects of LEE011 when given either alone or in
combination with other drugs. A combination of drugs might result in serious or
even life-threatening side effects. Some over the-counter and prescription
medications can reduce the effectiveness or increase the side effects of
LEE011. Likewise, LEE011 can increase the side effects or lessen the
effectiveness of some medications. This might result in serious or even
life-threatening side effects.

Procedures: pain, minor bleeding, bruising, possible infection