A PHASE 1, OPEN-LABEL, NON-RANDOMIZED, 2-PERIOD, FIXED SEQUENCE STUDY TO INVESTIGATE THE ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF 14C-PF-06835919 AND TO ASSESS THE ABSOLUTE BIOAVAILABILITY AND FRACTION ABSORBED OF PF-06835919 IN HEALTHY MALE PARTICIPANTS USING A 14C-MICROTRACER APPROACH.

PF-06835919 is an investigational compound that may eventually be used for the
treatment of non-alcoholic steatohepatitis (NASH), a liver disease. NASH is
characterized by inflammation (localized reaction that produces redness,
warmth, swelling, and pain) and the build-up of fat in the liver. There are no
therapies currently approved for the treatment of NASH.

PF-06835919 is a potent, reversible inhibitor of the enzyme ketohexokinase
(KHK) that is currently being developed for the treatment of NASH. KHK is the
enzyme (a protein that speeds up a chemical reaction in the body) responsible
for the first step of fructose metabolism (break down). By blocking fructose
metabolism, KHK may have the potential to reduce liver fat and inflammation.

The purpose of this study is to investigate how quickly and to what extent
PF-06835919 is absorbed and eliminated from the body.
PF-06835919 will be labelled with Carbon-14 (14C) and is thus radioactive. In
this way, PF-06835919 can be traced in blood, urine, and feces.

This study will also investigate how safe the new compound PF-06835919 is and
how well it is tolerated when it is administered to healthy volunteers. In
addition, the taste of the oral solution of PF-06835919 will be assessed. PF
06835919 has been administered to humans before.

This study will be performed in 6 healthy male volunteers.

The participation from screening until the final follow-up phone call will last
about 20 weeks.

The actual study will consist of 2 periods. Day 1 is the day of administration
of the study compound in each period. In both periods, the volunteers are
expected at the research center at 14:00 h in the afternoon 1 day before the
administration of study compound (so on Day -1). The time of entry may be
changed.

During Period 1, they will stay in the research center for a minimum of 8 days
(7 nights) and a maximum of 15 days (14 nights).

The amount of radioactivity in urine and feces will be measured daily from Day
1 onwards. If, from Day 7 onwards, the radioactivity levels in urine and feces
are below the pre-defined levels, volunteer will be allowed to leave the
research center in the afternoon. The discharge criteria are met when more than
90% of the administered radioactivity has left the body or less than 1% of
radioactivity is excreted in a 24-hour period on 2 consecutive days, and if
there are no medical objections. In Period 1, the volunteer will leave the
research center no later than Day 14. There are approximately 10 to 17 days
between administration of the study compound in Period 1 and administration of
the study compound in Period 2. In Period 2, the volunteer will leave the
research center on Day 5.

When the volunteer enters the research center, 2 coronavirus samples will be
collected at the same time to test if the volunteer is a carrier of SARS-CoV-2.
The coronavirus test will be done on the following days:
Day -1 of each period
Day 2 of each period
Before leaving the research center in Period 2
It may be decided that more tests are needed (eg, if the volunteer has COVID 19
symptoms).

In Period 1 on Day 1, the volunteers will be given 300 mg of 14C-labeled
PF-06835919 as an oral suspension of 100 mL. After administration of the study
compound, the vial will be rinsed 3 times with approximately 47 mL of water,
which the volunteers will also be required to drink.

In Period 2 on Day 1, they will be given 300 mg PF-06835919 without the
radioactive label as an oral suspension of 240 mL. Approximately 1 hour later,
they will receive 100 microgram (µg) PF-06835919 with radioactive label as an
intravenous infusion of 10 mL. The infusion will last about 15 minutes.

During the first 4 hours after oral administration of the study compound, they
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 study compound.

All volunteers will receive the same treatment.

The following side effects (non-severe and non-serious) have been reported in
at least 2 participants treated with PF-06835919, when given alone, in any
single human study completed to date:
- Headache
- Low blood sugar
- Acne
- Abdominal pain, discomfort and/or distension
- Change in bowel habit
- Constipation
- Loose stools
- Joint or muscle pain
- Pain in hands or feet
- Dry mouth
- Dry skin
- Rash or itch
- Difficulty sleeping
- Fatigue
- Increased urinary frequency
- Urinary tract infections

Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, there will taken about 440 milliliters (mL) of blood from the
volunteer. This amount does not cause any problems in adults.

To make a heart tracing, electrodes (small, plastic patches) will be pasted at
specific locations on the arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).

A sample for the coronavirus test will be taken from the back of ther nose and
throat using a swab. Taking the sample 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 the volunteer to gag. When the sample is taken from the
back of the nose, they may experience a stinging sensation and the eyes may
become watery.