A PHASE 1, OPEN-LABEL STUDY OF THE ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF 14C-LABELED IPI-145 AND THE ABSOLUTE BIOAVAILABILITY OF IPI-145 IN HEALTHY SUBJECTS

IPI-145 is a new investigational compound that may eventually be used for the
treatment of inflammatory diseases. The study medication inhibits the action of
specific proteins found in white blood cells. As white blood cells play a role
in the immune system, IPI 145 may influence specific parts of the immune
system. As such, it may be used in the treatment of inflammatory disorders and
also of blood malignancies. IPI-145 is not registered as a drug but has been
given to humans before.

Primary:
To evaluate the absorption, distribution, metabolism and excretion of IPI-145
following a single oral dose of 14C0IPI-145.
To determine the absolute bioavailability of IPI-145 following a single oral
dose of IPI-145 and an intravenous microdose of 14C-IPI-145

Secondary:
To assess the safety and tolerability of IPI-145 following a single dose
administration

Procedures and assessments:
Screening and follow-up: physical examination, vital signs (weight, body
temperature, blood pressure), pulse rate, clinical
laboratory (serum chemistry, haematology and urinalysis), and ECG

Only at screening: demography, medical history, prior and concomitant
medication, HBsAg, anti HCV, anti-HIV *, alcohol
and drug screen, quantiferon test body height

Repeated at entry op Day -1: alcohol and drug screen, vital signs (body
temperature, blood pressure), pulse rate, clinical laboratory (serum chemistry,
haematology and urinalysis), ECG

Period 1
Blood samples:
For PK IPI-145: pre-dose and until 3 days post-dose

Period 2
Blood samples:
For PK IPI-145, total radioactivity and metabolite profiles: pre-dose and until
8 days post-dose, with a possible extension
up to Day 15 post-dose, maximally

Urine collection:
For PK IPI-145, total radioactivity and metabolite profiles: Day 1-8 with a
possible extension up to Day 15 maximally. When discharge criteria are not met
on Day 15 a sample should be collected every 2-3 days until the criteria are
met.

Feces collection:
For PK IPI-145, total radioactivity and metabolite profiles: Day 1-8 with a
possible extension up to Day 15 maximally. When discharge criteria are not met
on Day 15 a sample should be collected every 2-3 days until the criteria are
met.

Period 1:
A single oral dose of 25 mg IPI-145 as a capsule, followed by a 15-minute IV
infusion of 2.8 µg 14C-IPI-145 with a tracer amount of radioactivity (14.8 kBq).

Period 2:
A single oral dose of 25 mg 14C0IPI-145 as oral supsension, containing 3.15 MBq
of radioactivity

The most important adverse events that were reported in previous studies:
rhinitis, headache, myalgia and reactions at injection sites.
Given the expected activity of the study medication you will be watched closely
for symptoms of infections though no increase in infections was observed in
either of the studies.
In this study, radio-labeled IPI-145 will be used. The amount of radioactivity
in the iv medication administered in Period 1 will be 14.8 KBq (KBq =
kiloBecquerel, this is a unit to express the amount of radioactivity in the
study drug). The amount of radioactivity in the oral medication administered in
Period 2 will be 3.15 MBq (MBq = megaBecquerel, this is a unit to express the
amount of radioactivity in the study drug, 1000 times the amount of 1 kBq). 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 14.8 KBq 14C labeled IPI-145 in Period 1 is
calculated to be negligible (that is, less than the natural background
radiation in one month). The additional radiation burden in this study due to
the administration of 3.15 MBq 14C labeled IPI-145 in Period 2 is calculated to
be 1 mSv. This is approximately 50 % of the average annual radiation burden.

Procedures: pain, light bleeding, heamatoma, possibly an infection

Registration of adverse effects: During the entire investigation all adverse
effects will be documented.