A randomized, open-label, 4-group, 2-period replicate design study to evaluate within- and between-subject variability in exposure of two lots of E5501 20 mg tablets administered as single doses of 40 mg, in the fasted and fed conditions to healthy subjects.

The drug to be given is an *investigational drug*. *Investigational* means that
the drug being tested in this study has not been approved by the United States
Food and Drug Administration (FDA) or the European Medicines Agency (EMA). The
drug is being developed for treatment of thrombocytopenia (low blood platelet
numbers). Platelets are blood cells that are involved in blood clotting; when
platelet numbers are low, the blood doesn*t clot normally and there is an
increased risk of bleeding. This drug is expected to improve the clotting of
the blood. The drug is still being researched.

Primary :
to determine whether concomitant administration of the study drug with food
reduces within- and between-subject variability in exposure as measured by area
under the plasma concentration-time course profile (AUC) and maximum observed
plasma concentration (Cmax).

Secondary :
to evaluate the bioavailability (BA) of the study drug 20 mg tablet Lot
P01008ZZA (test) relative to the study drug 20 mg tablet Lot P01009ZZA
(reference) under fasted and fed conditions to evaluate the overall effect of
food on the BA of the study drug relative to the fasted condition.

Design :
A randomized, open-label, 4-group, 2-period replicate design study to evaluate
within- and between-subject variability in exposure of two lots of study drug
20 mg tablets administered as single doses of 40 mg, in the fasted and fed
conditions to healthy subjects.; a washout of at least five days between dosing.

In total 4 Groups of 21 subjects will participate.

Groep A: 21 subjects will receive batch 1 (Lot P01008ZZA) of the drug on Day 1
and Day 6 underfasted conditions
Groep B: 21 subjects will receive batch 1 (Lot P01008ZZA) of the drug on Day 1
and Day 6 fed conditions
Groep C: 21 subjects will receive batch 2(Lot P01009ZZA) of the drug on Day 1
and Day 6 underfasted conditions
Groep D: 21 subjects will receive batch 2 (Lot P01009ZZA) of the drug on Day 1
and Day 6 fed conditions

After a screening visit the subjects will be in-house for a total of 11 Days,
followed by 8 short visits and end with a follow-up visit 2 Days after the last
ambulantory visit.

Procedures and assessments:
Screening and follow up: clinical laboratory, vital signs, physical
examination, weight, ECG, serum pregnancy test (females only); at eligibility
screening: medical history, height, urine alcohol and drug screen, HBsAg, anti
HCV, anti-HIV 1/2; vital signs, physical examination, 12-lead ECG, urine
pregnancy test (females only), clinical laboratory, urine alcohol and drug
screen to be repeated upon admission
follow-up on Day 35

Observation period:
one period in clinic from -17 h before drug administration on Day 1 up to 96 h
after drug administration on Day 6 and ambulatory visits on Days 12, 13, 16,
19, 22, 26, 29 and 33 (Treatment Period 2 starts on Day 6)

Blood sampling:
for pharmacokinetics of the study drug in plasma: pre-dose and 1, 2, 3, 4, 5,
6, 7, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose on Day 1 (Treatment Period
1) and pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, 12, 18, 24, 36, 48, 72 and 96 h
post-dose on Day 6 (Treatment Period 2)
for platelet counts: pre-dose and 48, 72 and 96 h post-dose on Day 1 (Treatment
Period 1) and pre-dose and 48, 72 and 96 h post-dose and once on Days 10, 12,
13, 16, 19, 22, 26, 29 and 33 (Treatment Period 2)

Safety:
adverse events: throughout the study; vital signs: once on Days -1, 1, 6, 10,
12, 13, 16, 19, 22, 26, 29 and 33; abbreviated physical examination: once on
Days -1 and 10; ECG: once on Days -1 and 10; clinical laboratory: once on Days
-1 and 10

Bioanalysis:
analysis of plasma study drug samples using a validated method by Sponsor
platelet count determinations by Sponsor

Study Medication
Active substance : E5501
Activity : c-Mpl agonist
Indication: adult chronic immune thrombocytopenic purpura (ITP),
thrombocytopenia associated with chronic liver disease (TLD) and prevention and
treatment of chemotherapy-induced thrombocytopenia
Strength : 20 mg
Dosage form : Lot P01008ZZA and Lot P01009ZZA tablets

Treatments
Treatment A: a single oral dose of 40 mg (2 x 20 mg tablets) Lot P01008ZZA in
the fasted state in each period
Treatment B: a single oral dose of 40 m (2 x 20 mg tablets) Lot P01008ZZA in
the fed state in each period
Treatment C: a single oral dose of 40 mg (2 x 20 mg tablets) Lot P01009ZZA in
the fasted state in each period
Treatment D: a single oral dose dose of 40 mg (2 x 20 mg tablets) Lot
P01009ZZA in the fed condition in each period

Each subject will be dosed for 2 periods.

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