A PHASE I, RANDOMIZED, DOUBLE BLIND PLACEBO * CONTROLLED, SINGLE AND MULTIPLE DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF OCID 2987 IN HEALTHY MALE SUBJECTS

The drug to be given, OCID 2987, is a new, investigational compound that may
eventually be used for the treatment of asthma and COPD (chronic obstructive
pulmonary disease).
OCID 2987 inhibits i.e., reduces the activity of an enzyme called PDE4.
Inhibition of this enzyme reduces the number and activity of a number of White
blood cells in the body, mainly the neutrophils, eosinophil*s and macrophages
(these are the different type of white cells in the normal human blood) all of
which cause inflammation (usual response by the human body to infection, injury
or allergy) in the lungs.
OCID 2987 is a PDE4 inhibitor which has shown to have significant
anti-inflammatory activity in animal studies in our laboratory. It is known
that increase in these above mentioned cells in the lung can worsen the
symptoms of these patients with COPD and Asthma.
In this way, OCID 2987 is a potential therapy for chronic pulmonary conditions,
such as asthma and COPD.

Primary:
-To determine the safety and tolerability of ascending single and multiple oral
doses of OCID 2987 in healthy male subjects.

Secondary:
-To determine the pharmacokinetics (PK) of single and multiple oral dose OCID
2987 in healthy male subjects.
-To assess the pharmacodynamic (PD) response to single and multiple oral doses
of OCID 2987 in healthy male subjects.
-To profile plasma samples in selected cohorts for presence of circulating
metabolites using qualitative or semi-quantitative analytical approaches.

Design:
a double-blind, randomized, placebo-controlled, sequential group, single- and
multiple-ascending dose study; Part 1 (SAD) consists of six groups of eight
healthy male subjects each receiving a single oral dose of OCID 2987 or placebo
(six verum and two placebo); Part 2 (MAD) consists of three groups of eight
healthy male subjects each receiving an oral dose of OCID 2987 or placebo (six
verum and two placebo) once or twice daily for fourteen days

Procedures and assessments
Screening and follow-up:
clinical laboratory, vital signs, physical examination, ECG, weight; at
eligibility screening: medical history, urine alcohol and drug screen, cotinine
screen, HBsAg, anti HCV, anti-HIV 1/2; physical examination, vital signs, ECG,
urine alcohol and drug screen, cotinine screen and clinical laboratory to be
repeated upon admission

Part 1 (SAD)
Observation period :one period in clinic from -17 h up to 48 h after drug
administration

Blood sampling:
- for pharmacokinetics of OCID 2987 in plasma: pre-dose and 0.5, 1, 1.5, 2, 3,
4, 5, 6, 8, 10, 12, 16, 24 and 48 h post-dose
- for pharmacodynamics of OCID 2987 in plasma: pre-dose and 2, 4, 8, 24 h
post-dose
- Urine sampling:for pharmacokinetics of OCID 2987: pre-dose and intervals 0-4,
4-8, 8-12 and 12-24 h post-dose

Safety assessments:
adverse events: throughout the study and specifically at pre-dose and 0.5, 1,
2, 4, 6, 12, 24 and 48 h post-dose;
physical examination: once on Day 2;
vital signs (including temperature; supine and standing): pre-dose and 0.5, 1,
2, 4, 8, 12, 24 and 48 h post-dose;
clinical laboratory: once on Day 2;
12-lead ECG: pre-dose and 1, 2, 4, 8, 24 and 48 h post-dose;
Cardiac monitoring: from -30 min to 4 h post-dose

Part 2 (MAD)
Observation period: one period in clinic from -17 h before drug administration
on Day 1 up to 48 h after last drug administration on Day 14

Blood sampling:
- for pharmacokinetics of OCID 2987 in plasma: pre-dose and 0.5, 1, 1.5, 2, 3,
4, 5, 6, 8, 10, 12, 16 h post-dose on Day 1, pre-dose on Days 2-13, pre-dose
and 0.5, 1,1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 h post-dose on Day 14
- for pharmacodynamics of OCID 2987 in plasma: Day 1 and Day 14: pre-dose and
2, 4, 8, 24 h postdose
- Urine sampling: for pharmacokinetics of OCID 2987:pre-dose and intervals 0-4,
4-8, 8-12 and 12-24 h post-dose on Days 1 and 14

Safety assessments:
adverse events: throughout the study and specifically at pre-dose and 0.5, 1,
2, 4, 6 and 12 h post-dose on Day 1, pre-dose on Days 2-13 and pre-dose and
0.5, 1, 2, 4, 6, 12, 24, 48 h post-dose on Day 14;
physical examination: once on Day 16;
weight: once on Days 3, 5, 7 and 14;
vital signs (including temperature; supine and standing): pre-dose and 0.5, 1,
2, 4, 8 and 12 h post-dose on Day 1, pre-dose and expected tmax on Days 2-13
and pre-dose and 1, 2, 4, 8, 12, 24 and 48 h post-dose on Day 14;
clinical laboratory: pre-dose on Days 1, 7 and 14 and once on Day 16;
ECG: pre-dose and 1, 2, 4, 8 and 24 h post-dose on Day 1, pre-dose on Days 3,
5, 7 and 10, pre-dose and 1, 2, 4, 8, 24 and 48 h post dose on Day 14;
cardiac monitoring: from -30 min to 4 h post-dose on Days 1 and 14

Bioanalysis: analysis of plasma and urine OCID 2987 samples using validated
methods by PRA

Active substance: OCID 2987

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