A phase 1, open label, 2-period, fixed sequence, study to assess the mass balance, absolute bioavailability of 14C-PF-06826647 in healthy male participants

PF-06826647 is a new experimental compound that may potentially be used for the
treatment of the skin diseases psoriasis and hidradenitis suppurativa, and the
digestive tract conditions that are part of inflammatory bowel disease (IBD).
Cytokines are chemical messengers that help control the immune system and fight
diseases. Some of these cytokines play an important role in the progression of
these diseases. PF-06826647 is a molecule that has the potential to reduce the
activity of these cytokines and may therefore be a treatment option for these
diseases.

The purpose of this study is to investigate how quickly and to what extent
PF-06826647 is absorbed and eliminated from the body (pharmacokinetics).
PF-06826647 will be labelled with Carbon-14 (14C) and can be traced in blood,
urine, and feces.

This study will also investigate how safe the new compound PF-06826647 is and
how well it is tolerated when it is administered to healthy volunteers. In
addition, the taste of the oral solution of PF-06826647 will be assessed. PF
06826647 has been administered to humans before.

The study will last about 11 weeks.

The study consist of 2 periods. Day 1 is the day of administration of the study
compound in each period. During Period 1, the volunteer will stay in the
research center for a minimum of 6 days (5 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 5 onwards, the radioactivity levels in urine
and feces are below the pre-defined levels, the volunteer is allowed to leave
the research center. If the discharge criteria are not met until Day 13 in
Period 1, the volunteer will stay in the research center and Period 2 will
start the next day. Period 2 will start at least 14 days after administration
of the study compound in Period 1. In Period 2, the volunteer will leave the
research center if the stay in Period 2 equals the period of stay in Period 1.
Volunteer will receive a follow-up phone call at least 28 days after the last
administration of the study compound in Period 2.

When the volunteer enters the research center, two 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 each Period
It may be decided that more tests are needed.

In Period 1 on Day 1, volunteer will be given 600 mg of 14C-labeled PF-06826647
as a drink of 100 mL. After administration of the study compound, the cup will
be rinsed 3 times with 47 mL of water, which the volunteer will also be
required to drink.

In Period 2 on Day 1, volunteer will be given 600 mg PF-06826647 without the
radioactive label as 6 tablets that contain 100 mg PF-06826647 each. The
tablets will be ingested with a minimum of 240 mL of water. If necessary
additional water to ingest the tablets is allowed. After ingestion of the
tablets, one of the investigators will inspect volunteers hands and mouth to
check whether volunteer ingested the tablets. Approximately 3 hours later,
volunteer will receive 100 microgram (µg) PF-06826647 with radioactive label as
an intravenous infusion of 20 mL. The infusion will last about 1 hour.

During the first 4 hours after taking the drink containing the study compound,
volunteer 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.

PF-06826647 has been studied in animals and humans, but not all product safety
information is known at this time. There may be rare and unknown side effects,
including serious or severe reactions that have not yet been discovered.

Human studies with PF-06826647 consist of one completed Phase 1 study
(C2501001). A total of 69 healthy participants volunteers and 40 patients with
plaques psoriasis received study treatments. All reported adverse events were
mild in severity except for one adverse event that was moderate in a psoriasis
patient receiving placebo. There were no serious or severe adverse events
observed.

Animal studies have been conducted in animals to try to identify risks that may
occur in people given PF-06826647. In some animals given high doses of
PF-06826647, increases in blood pressure and heart rate occurred. Some animals
had discolored feces and gastric reflux. These effects occurred generally at
high dose levels of PF-06826647.
Based on animal studies, PF-06826647 may increase levels of certain proteins in
the blood, which may indicate inflammation or injury to the liver. Rats and
monkeys given PF-06826647 had increases in liver enzymes. However, these
increases were not associated with signs of liver injury in animals. There is
also the potential for changes in blood lipid levels (cholesterol and
triglycerides) with PF-06826647. Lipid changes seen in animals were small and
not associated with evidence of liver or other tissue injury. Decreases in
certain immune cells (white blood cells) also occurred in some animals
receiving PF-06826647. These immune cells normally help protect against
infection.

Potential Side Effects:

Reactivation of viruses:
Certain viruses can remain in a sleeping form in the body and they may
reactivate and cause negative effects. In studies with PF-06826647 or other
similar medications, reactivation of the chicken pox virus (herpes zoster) has
caused shingles and reactivation of the herpes simplex virus has caused cold
sores or fever blisters in the mouth or genital ulcers. It is not known if
PF-06826647 could lead to the reactivation of hepatitis viruses. Volunteer will
not be allowed to participate in the study if the blood tests show that
volunteer have had hepatitis types B or C viruses (unless demonstrated to be
completely cured from Hepatitis C).

Serious or Unusual infections:
PF-06826647 is a study drug that affects your immune system. It may lower the
ability of your body to fight infections, leading to more serious infections or
infections that usually don*t occur in people with a normal immune system.
There were no infections observed in the previous healthy volunteer study with
PF-06826647. Some people have had serious infections or unusual infections
while taking medications similar to PF-06826647. Volunteer should not start
PF-06826647 if volunteer have any kind of infection.

Cancer:
PF-06826647 may increase the risk of certain cancers by changing the way the
immune system defends against cancer. No formation of cancers has been reported
in the previous healthy volunteer study with PF-06826647. Lymphoma and other
cancers, including skin cancers, have been reported in patients taking
medications that work in a similar way to PF-06826647. Most people with a
history of cancer will not be eligible for this study, except for those who
have had successfully treated skin cancers that were not of the melanoma type.

Changes in certain laboratory test results. Some changes in blood tests that
have occurred in animal or human studies with PF-06826647:
•Decreases in lymphocyte counts.
•Decreases in neutrophil counts.
•Increases in platelet counts.
•Changes in other laboratory tests, such as a rise in muscle enzymes (creatine
kinase), kidney function parameters (serum creatinine), blood cholesterol or a
drop in hemoglobin (red blood cells) levels.

Deep vein thrombosis and pulmonary embolism:
Pulmonary emboli have occurred in patients taking medications that work in
similar ways to PF-06826647. PF-06826647 may increase the risk of developing a
blood clot, including in legs (deep vein thrombosis) and lungs (pulmonary
embolism). A serious adverse event of deep vein thrombosis occurred in a female
healthy volunteer taking both PF-06826647 600 mg daily and high dose oral
contraceptive (30 µg ethinyl estradiol + 150 µg of levonorgestrel) daily in
C2501005, a Phase 1 Drug-Drug Interaction Study. If volunteer have had a
history of recent blood clots in legs or lungs or a history of repeated blood
clots in legs or lungs, or have other risk factors for clotting, volunteer may
not be eligible for this study.

Possible discomforts:
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, about 390 milliliters (mL) of blood will be taken from the volunteer.

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

Radiation:
This study involves using radioactive markers. The additional amount of
radiation the volunteer will be exposed to in this study is below 0.1 mSv.

A sample for the coronavirus test will be taken from the back of the 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, the volunteer may experience a stinging sensation and the
eyes may become watery.