A Microdose Study to Describe the Intravenous Pharmacokinetics of [14C]-GSK2239633 in Healthy Male Subjects.

The drug to be given GSK2239633 is a new, investigational compound that may
eventually be used for the treatment of asthma.
Asthma is characterized by a predisposition to chronic inflammation of the
lungs in which, amongst other things, the airways (bronchi) are narrowed.
During asthma attacks (exacerbations of asthma), the smooth muscle cells in the
bronchi constrict, the airways become inflamed and swollen, and breathing
becomes difficult. GSK2239633 is expected to block inflammatory cells which are
involved in allergic inflammation and as such may be beneficial for asthma
patients.

Primary:
To investigate the intravenous pharmacokinetics of [14C]-GSK2239633 in healthy
male subjects
To compare total radioactivity (drug-related material) in plasma relative to
parent plasma concentration
To determine total radioactivity (drug-related material) in urine

Secondary:
To generate samples that may be used for metabolite profiling under a separate
protocol

Design:
A single-dose, single period, microdose study in six healthy male volunteers
receiving an iv microdose of [14C]-GSK2239633, containing approximately 10 kBq
(270.3 nCi) radiocarbon.

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

Observation period:
One period in clinic from -17 h up to 48 h after drug administration.

Blood sampling:
For pharmacokinetics of GSK2239633 in plasma and total radioactivity: at
screening, upon admission and immediately pre-dose and 0 (immediately after
start infusion), 5, 10 and 15 (immediately after completion of iv dosing)
minutes after start of infusion and 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4,
6, 8, 12, 16, 24, 30, 36 and 48 hours after end of infusion.

Urine sampling:
For pharmacokinetics and total radioactivity: pre dose sample and interval 0-24
h post dose.

Safety assessments:
Adverse events: throughout the study; vital signs pre dose and 45 minutes 12,
24 and 48 h post dose; ECG: pre-dose and 15 minutes after start infusion and
15, 45 minutes and 12 and 48 h after end of infusion; Telemetry from pre dose
until 8 h post dose; clinical laboratory pre dose and 24 and 48 h post end of
infusion; liver function tests (ALT, AST, alkaline phosphatase, bilirubin) will
be taken ~18 hours post-dose for the first subject only so the results can be
reviewed prior to dosing subsequent subjects

Bioanalysis:
Analysis of plasma and urine GSK2239633 samples using a validated method by
Sponsor.
Analysis of total radioactivity in plasma and urine using a validated method by
Sponsor.

Active substance: GSK2239633 and [14C]-GSK2239633

Activity: CCR4 antagonist selectively blocking recruitment of TH2 cells which
are effectors cells for allergic inflammation

Indication: Asthma
Strength: 10 µg/mL
Dosage form: iv infusion (30 mL)

Treatment: a single 15 min iv infusion of 100 µg [14C]-GSK2239633, containing
approximately 10 kBq (270.3 nCi) radiocarbon, on Day 1

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

Medication:
Since GSK2239633 will be administered to man for the first time in this study,
to date adverse effects in man have not yet been reported. In previous studies
with rats and dogs, in which GSK2239633 was administered in very high single
doses, no relevant adverse events were reported. As this study is the first
administration to man of GSK2239633, safety and tolerability will be monitored
closely.