EVALUATION OF SAFETY, TOLERABILITY AND PHARMACOKINETIC CHARACTERISTICS OF MULTIPLE-ASCENDING DOSES OF CG400549 IN HEALTHY VOLUNTEERS

The study medication to be administered, CG400549 is a new, investigational
compound that may eventually be used for the treatment of infections caused by
methicillin-resistant Staphylococcus aureus (MRSA). MRSA is a microbe, which is
resitent for most of the common antibiotics. Because of this resistance, MRSA
is difficult to treat.

For survival, microbes (bacteria) need an intact cell wall. CG400549
specifically inhibits the synthesis of the cell wall for all kinds of bacteria;
as a consequence, bacteria will not survive. As CG400549 differentiates itself
from other antibacterial agents through its novel mechanism of action, it may
eventually be used to treat infections cuased by resistant bacteria, such as
MSRA

The purpose of the study is to investigate how safe the compound is and how
well the compound is tolerated. The study will also investigate how quickly and
to what extent the compound is absorbed and eliminated from the body (this is
called pharmacokinetics).

Design
This is a Phase 1, 3 cohorts study consisting of a randomised, double-blind,
and placebo-controlled design., each cohort will consist of 8 healthy male
subjects., Subjects in Group 1 will receive an oral dose of CG400549 or placebo
(six verum and two placebo) twice daily on Days 1-5 and a final oral morning
dose of CG400549 or placebo on Day 6; subjects in Groups 2 and 3 will receive a
single oral dose of CG400549 or placebo (six verum and two placebo) on Day 1,
an oral dose of CG400549 or placebo twice daily on Days 3-7 and a final oral
morning dose of CG400549 or placebo on Day 8. The safety and PK data from each
cohort will be reviewed before advancing to the next cohort.

Screening and Follow up
physical examination, 12-lead electrocardiogram (ECG), clinical laboratory
(clinical chemistry, haematology, coagulation, thyroid function and
urinalysis), vital signs (including supine systolic and diastolic blood
pressure, pulse rate and oral body temperature), adverse event (AE) assessments
and previous and concomitant medication at eligibility screening only: informed
consent; inclusion/exclusion criteria; demographics; medical history; height
and weight; drug, alcohol, and nicotine screen; testing for hepatitis B surface
antigen (HBsAg), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
1/2. On admission: physical examination, vital signs, 12-lead ECG, clinical
laboratory (clinical chemistry, haematology, coagulation, thyroid function and
urinalysis) and alcohol, drug, and nicotine screen.

Observation period

Blood sampling
For PK of CG400549 in plasma:
Cohort 1 : pre-dose (D1), 12 h (D1), 24 h (D2), 36 h (D2), 48 h (D3), 60 h
(D3), 72 h (D4), 84 h (D4), 96 h (D5), 108 h (D5), 120 h (D6), 120.25h (D6),
120.5 h (D6), 121 h (D6), 121.5 h (D6), 122 h (D6), 122.5 h(D6), 123 h (D6),
124 h (D6), 125 h (D6), 126 h (D6), 128 h (D6), 130 h (D6), 132 h (D6), 144 h
(D7), 156 h (D7), 168 h (D8),

Cohort 2 and 3 : pre-dose and 0.25 h, 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h,
5 h, 6 h, 8 h, 10 h, 12 h, 24 h (D2), 36 h (D2), 48 h (D3), 60 h (D3), 72 h
(D4), 84 h (D4), 96 h (D5), 108 h (D5), 120 h (D6), 132 h (D6), 144 h (D7), 156
h (D7), 168 h (D8), 168.25h (D8), 168.5 h (D8), 169 h (D8), 169.5 h (D8), 170 h
(D8), 170.5 h(D8), 171 h (D8), 172 h (D8), 173 h (D8), 174 h (D8), 176 h (D8),
178 h (D8), 180 h (D8), 192 h (D9), 204 h (D9), 216 h (D10).

Urine sampling
For PK of CG400549 in urine
Cohort 1: pre-dose (point sample) and in intervals of 120-124, 124-128, 128
132, 132 144, 144 156 and 156-168 h post-dose

Cohort 2 and 3: pre-dose (point sample) and in intervals of 0-4, 4-8, 8 12, 12
24, 24 36, 36-48, 168-172, 172-176, 176-180, 180-192, 192-204 and 204-216 h

Safety assessments
AEs: recorded from the time the Informed Consent Form is signed until
completion of the follow up visit;
Cohort 1 : physical examination: Day -1~8 and D15; clinical laboratory
(clinical chemistry, haematology, coagulation, thyroid function and
urinalysis): once on Days -1, 3, 5, 8 and 15; 12 lead ECG: On Day 1, at 30 min
pre-dose and 4, 8, 12, and 24 h, On Day 2~5 at 4, 8, 12 and 24h. On Day 6 at 1,
4, 8, 12, 24 and 48h and Day 15; weight: Days -1; vital signs: On Day 1, at
pre-dose and 4, 8, 12 and 24h. On Day 2~5 at 4, 8, 12 and 24h. On Day 6, at
0.5, 1, 2, 4, 8, 12, 24, 28, 32, 36 and 48 h and Day 15,

Cohort 2 and 3 : physical examination: Day -1~10; clinical laboratory (clinical
chemistry, haematology, coagulation, thyroid function and urinalysis): once on
Days -1, 3, 5, 8 and 10; 12 lead ECG: On Day 1, at 30 min pre-dose and 1, 4, 8,
12, 24 and 48h, On Day 3~7 at 4, 8, 12 and 24h. On Day 8 at 1, 4, 8, 12, 24 and
48h and Day 17; weight: Days -1; vital signs: On Day 1, at pre-dose and 0.5, 1,
2, 4, 8, 12, 24, 28, 32, 36 and 48 h, On Day 3~7 at 4, 8, 12 and 24h. On Day 8
at 0.5, 1, 2, 4, 8, 12, 24, 28, 32, 36 and 48 h and Day 17

Active medication
Active substance: CG400549
Activity: enoyl-acyl-carrier-protein reductase (Fabl) inhibitor
Indication: methicillin-resistant Staphylococcus aureus
Strength: 160mg
Dosage form: oral capsule

Placebo
Substance: microcrystalline cellulose, sodium stearyl fumarate
Activity: none
Indication: not applicable
Strength: not applicable (to appear identical to 160mg active capsules)
Dosage form: oral capsule

Procedures: pain, light bleeding, haematoma and infection