An open-label, single-dose study to assess the relative bioavailability of 2 new formulations of UCB5857 versus the reference formulation, and to evaluate the mass balance recovery and the absolute bioavailability of UCB5857 using intravenous and oral microtracers in healthy subjects

UCB5857 is a new investigational compound that may eventually be used for the
treatment of autoimmune diseases. Autoimmune diseases arise from an abnormal
immune response of the body against substances and tissues normally present in
the body. Examples of autoimmune diseases are rheumatoid arthritis and
Sjögren*s syndrome. UCB5857 inhibits the action of a specific protein,
phosphoinositide 3 kinase-delta, found in white blood cells. White blood cells
play an important role in the immune system (body defense system). Due to its
working mechanism, UCB5857 may reduce inflammatory reactions by inhibiting the
action of phosphoinositide 3 kinase-delta in white blood cells.

The Purpose of the study is to determine how quickly and to what extent two new
formulations of UCB5857 (formulation A and B, administered by mouth) are
absorbed and distributed into the body and how fast these are metabolized
(broken down) and eliminated from the body compared to a previously studied
formulation of UCB5857 (reference formulation).

The compound to be administered will be labeled with a low dose of 14 Carbon
(14C) and is thus radioactive (also called radiolabeled). This enables the
investigator to trace the compound in blood, urine, and feces. The safety and
tolerability of UCB5857 will be also assessed throughout the study.

The actual study will consist of 3 treatment periods.

If the volunteer participate in Period 1a, he/she will stay in the clinical
research center in Zuidlaren for 3 periods. In Period 1a, the volunteer will
stay in the clinical research center for 6 days (5 nights). In Periods 2 and 3
you will stay in the clinical research center for 5 days (4 nights). The time
interval between each period is 2 days.

If the volunteer participate in Period 1b, he/she will stay in the clinical
research center in Zuidlaren for 2 periods. For Period 1b and Period 2 the
volunteer will stay in the clinical research center for 1 interconnected period
of 13 days (12 nights); Period 2 will start immediately after completion of
Period 1. For Period 3 the volunteer will stay in the clinical research center
for 5 days (4 nights).
The time interval between Period 1b/2 and Period 3 is 2 days.

Participants in Period 1a will receive UCB5857 in the form of a capsule,
followed by administration of the radiolabeled study compound (14C UCB5857) via
an intravenous injection 4 hours after intake of the capsule. The duration of
the intravenous injection will be approximately 1 minute.

Participants in Period 1b will receive UCB5857 together with the radiolabeled
study compound (14C UCB5857) in the form of a capsule.

In Period 2 and 3, the volunteer will receive UCB5857 in the form of a capsule.

The study will consist of 3 treatment periods during which you will receive
UCB5857 in different formulations.

In Period 1 participants will be divided into Period 1a (6 participants) or
Period 1b (6 participants).
* Period 1a will consist of 6 days (Day -1 to Day 5). On Day 1 of Period 1a, 6
participants will receive a single dose of 30 milligram UCB5857 in the form of
a capsule. Four hours after intake of the capsule you will receive a single
dose of 20 microgram radiolabeled study compound (14C UCB5857) in the form an
injection into a vein in your arm (intravenous injection).
* Period 1b will consist of 9 days (Day -1 to Day 8). On Day 1 of Period 1b, 6
participants will receive a single dose of 30 milligram UCB5857 together with
20 microgram radiolabeled study compound (14C UCB5857) in the form of a
capsule.

Periods 2 and 3 each consist of 5 days (Day -1 to Day 4). On Day 1 of each
period all 12 participants will receive a single dose of 30 milligram UCB5857
(either formulation A or B) in the form of a capsule. In which sequence the
volunteer will receive these 2 formulations (A-B or B-A) will be determined by
chance.

All potential drugs cause adverse events; the extent to which this occurs
differs. In this study the volunteer will receive 30 mg UCB5857 in 3 different
formulations (formulation A, B, and the previously studied [reference]
formulation). In a previous study in healthy volunteers, who received the
reference formulation of UCB5857, no adverse effects were observed following
administration of single and multiple doses of UCB5857 at a dose level of 30
mg. Following single and multiple dose administration of UCB5857 at higher dose
levels (i.e., 60 mg and 90 mg) the most frequently observed adverse effects
were skin rash and gastrointestinal problems (abdominal discomfort, diarrhea,
nausea, vomiting), which were considered to be possibly related to the study
drug. Other adverse effects observed after intake of UCB5857 or placebo were:
headache, taste alteration (metallic taste), dizziness, sore throat, nasal
congestion, and tooth pain. All adverse effects observed were transient and of
mild or moderate intensity, except for 1 severe event of skin rash in 1
volunteer who had received a single dose of 90 mg UCB5857. The skin rash
observed in this volunteer was transient and had resolved at the end of the
study .

The adverse effects that may occur following intake of the new formulations A
and B are expected to be similar to the adverse effects observed after intake
of the reference formulation. However, you should be aware that the
aforementioned adverse effects and possibly other, still unknown adverse
effects, may occur during the study. With the dose used in this study (a single
dose of 30 mg) no serious adverse effects are expected.

In this study radiolabeled UCB5857 will be used in Period 1a and 1b. The amount
of radioactivity in this dose will be 74 kBq (kBq = kiloBecquerel, this is a
unit to express the amount of radioactivity in the study drug). The average
environmental background radiation burden in The Netherlands is approximately 2
mSv per year (mSv = miliSievert, this unit 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 74 KBq 14C-labeled UCB5857 is calculated to be negligible
(that is, less than the natural background radiation in 1 month).