A PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, ALTERNATING PANEL, SINGLE ASCENDING DOSE STUDY EVALUATING THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF JTK-656 AND THE EFFECT OF FOOD ON THE PHARMACOKINETICS OF JTK-656 IN HEALTHY MALE SUBJECTS

A randomized, double-blind, placebo-controlled, alternating panel, single
ascending dose study with four panels of nine subjects each. Subjects will
receive three single oral doses (Panels A, B and C) or two single oral doses
(Panel D) of JTK-656 or placebo. The subjects will receive medication under
fasting conditions, except in one period of Panel C where the medication will
be taken after an FDA high-fat breakfast. At each dose level, 6 subjects will
receive active drug and 3 subjects will receive placebo in a randomized
fashion. Subjects in Panels A and B will receive placebo once in the study and
active treatment twice. Subjects in Panel C will receive the same treatment
twice, once under fasting conditions and once after an FDA high-fat breakfast.
In Panels C and D, 6 subjects will receive placebo at least once and 3 subjects
will receive active treatment only. There will be a wash-out of at least ten
days between administrations within a panel.

Primary :To investigate the safety and tolerability of ascending single oral
doses of JTK-656 administered to healthy male subjects

Secondary:To determine the pharmacokinetics (PK) of ascending single oral doses
of JTK-656 administered to healthy male subjects (Part 2 only)
To determine the effect of food on the PK of JTK-656 administered under fed and
fasted conditions to healthy male subjects (Part 2, Panel C)

Part 1 (Period 1 of Panels A and B; Period 2 of Panel A)

Procedures and assessments

Screening and follow-up:Clinical laboratory, vital signs, physical examination,
12-lead electrocardiogram (ECG), weight and previous and concomitant
medication; at eligibility screening only: height, medical history, alcohol and
drug screen, cotinine test, hepatitis B surface antigen (HBsAg), anti hepatitis
C virus (HCV) and anti-human immunodeficiency virus (HIV) 1/2; at follow-up
only: adverse events (AEs)

Each admission :Alcohol and drug screen, cotinine test, vital signs, clinical
laboratory, brief physical examination, AEs and previous and concomitant
medication
Observation period :Each period in clinic from -17 h up to 24 h after drug
administration and an ambulatory visit on Day 8 (+/- 1 day) for follow-up

Safety assessments :AEs: throughout the study and specifically at pre-dose and
1, 2, 4, 8, 12 and 24 h post dose; weight: pre-dose; vital signs: pre-dose and
1, 2, 3, 4, 6, 8, 12 and 24 h post-dose; 12-lead ECG: pre-dose and 1, 4 and 24
h post-dose; clinical laboratory: pre dose and 24 h post-dose

Exploratory lipid profile assessments:HDL2-cholesterol and HDL3-cholesterol:
pre dose and 24 h post-dose
Bioanalysis:Analysis of serum exploratory lipid profile assessment samples
(HDL2-cholesterol and HDL3 cholesterol) by the contracted laboratory



Part 2 (Period 1 of Panels C and D; Period 2 of Panels B, C and D; Period 3 of
Panels A, B, and C)

Procedures and assessments

Screening and follow-up:Clinical laboratory, vital signs, physical examination,
12-lead ECG, weight and previous and concomitant medication; at eligibility
screening only: height, medical history, alcohol and drug screen, cotinine
test, HBsAg, anti HCV, anti-HIV 1/2; at follow-up only: AEs

Each admission :Alcohol and drug screen, cotinine test, vital signs, clinical
laboratory, brief physical examination, AEs and previous and concomitant
medication

Observation period :Each period in clinic from -17 h up to 48 h after drug
administration and an ambulatory visit on Day 8 (+/- 1 day) for follow-up
Blood sampling :For PK of JTK-656: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12,
24, 36 and 48 h post dose and at follow-up

Safety assessments :AEs: throughout the study and specifically at pre-dose and
1, 2, 4, 8, 12, 24, 36 and 48 h post-dose; weight: pre-dose; vital signs:
pre-dose and 1, 2, 3, 4, 6, 8, 12, 24 and 48 h post dose; 12-lead ECG: pre-dose
and 1, 4, 24 and 48 h post-dose; clinical laboratory: pre dose and 24 and 48 h
post-dose

Exploratory lipid profile assessments:HDL2-cholesterol and HDL3-cholesterol:
pre-dose and 24 and 48 h post-dose
Bioanalysis:Analysis of plasma JTK-656 samples using a validated high
performance LC-MS/MS method by Sponsor
:Analysis of serum exploratory lipid profile assessment samples
(HDL2-cholesterol and HDL3 cholesterol) by the contracted laboratory

Study Medication
Active substance :JTK-656
Activity :HIV integrase inhibitor
Indication :HIV-1 infection
Strength :0.3 mg/2 g PEG400, 1.5 mg/2 g PEG400 and 7.5 mg/2 g
PEG400 (Part 1) and 25 and 200 mg (Part 2)
Dosage form :Oral solution (Part 1) and tablet (Part 2)
Batch number :To be included in the clinical study report

Treatments

Part 1

Panel A : Period 1: a single oral dose of 0.3 mg JTK-656 or placebo in the
fasted state
Period 2: a single oral dose of 7.5 mg JTK-656 or placebo in the
fasted state

Panel B : Period 1: a single oral dose of 1.5 mg JTK-656 or placebo in the
fasted state



Part 2

Panel A : Period 3: a single oral dose of 75 mg JTK-656 or placebo in the
fasted state

Panel B : Period 2: a single oral dose of 25 mg JTK-656 or placebo in the
fasted state
Period 3: a single oral dose of 200 mg JTK-656 or placebo in the
fasted state

Panel C : One Period: a single oral dose of 400 mg JTK-656 or placebo in the
fasted state
One Period: a single oral dose of 400 mg JTK-656 or placebo in the fed
state
One Period: a single oral dose of 800 mg JTK-656 or placebo in the
fasted state

Panel D : Period 1: a single oral dose of 1200 mg JTK-656 or placebo in the
fasted state
Period 2: a single oral dose of 1600 mg JTK-656 or placebo in the
fasted state

Procedures: insertion of the dwelling canula/venapuncture: some pain, bruise,
light bleeding.

JTK-656:
adverse events in animal studies: vomiting, changes and increase of levels of
blood lipids at high doses.