An Open Label, Non-Randomized, Single dose, Mass Balance Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C-GSK2251052 Administered as a Single Intravenous Dose to Healthy Adult Subjects (LRS115243)

The drug to be given GSK2251052 is a new, investigational compound that may
eventually be used for the treatment of bacterial infections.
Bacteria are getting more and more immune to currently available antibiotics.
Thus there is a need for new drugs that can serve as antibiotics. Of GSK2251052
is expected that it stops the growth of bacteria by inhibiting the synthesis of
proteins the bacteria need to grow.

The purpose of the study is to investigate how quickly and to what extent
GSK2251052 is absorbed, distributed, metabolized (converted) and eliminated
from the body (this is called pharmacokinetics). The compound to be
administered will be labeled with 14-Carbon (14C) and is thus radioactive. This
enables the investigator to trace the compound in blood, urine and feces. The
safety and tolerability of the compound will also be evaluated.

Design:
open-label, non-randomized, mass-balance study in six healthy male subjects
receiving a single one hour iv infusion of [14C]-GSK2251052, containing
approximately 0.56 MBq

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

Observarion period:
one period in clinic from -17 h up to 336 h (Day 15) after drug administration
if total radioactivity in 2 consecutive 24-hour collections (288-312 hours
post-dose [Days 12-13] and 312-336 hours [Days 13-14] post-dose) in both urine
and faeces combined are * 1% of the administered dose. In the event that total
radioactivity in faeces and/or urine is >1% of the administered dose at 336
hours, subjects will be required to return to the unit every 168 hours (7 days)
or until the radioactivity excreted falls to *1% of the administered dose .

Blood sampling:
for pharmacokinetics of GSK2251051, metabolic profiling in plasma and total
radioactivity in plasma and whole blood: pre-dose prior to the start of
infusion, 0.5, 1 (just prior to the end of infusion) and 5, 15, 30 minutes and
2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, 168 and 192 hours
post-dose.

Urine sampling:
for pharmacokinetics of GSK2251051, total radioactivity and metabolic
profiling: pre-dose and intervals 0-6, 6-12, 12-24 and 24 h intervals up to
discharge

Feces sampling:
for pharmacokinetics of GSK2251051, total radioactivity and metabolic
profiling: pre-dose and 0-24 and 24 h intervals up to discharge

Safety assessments
adverse events: throughout the study; ECG: pre-dose, immediately after the end
of the infusion, 1 and 24 h after the end of infusion and once on Day 15; vital
signs: pre-dose (2x) and once on Day 15; clinical laboratory: once on Days 1, 2
and 15; physical examination: once on Day 15

Bioanalysis:
analysis of plasma, urine and faeces analysis of plasma, urine and faeces
GSK2251051 samples using validated methods by Sponsor
analysis of total radioactivity in plasma, urine, whole blood and faeces using
validated methods by PRA
metabolic profiling by Sponsor

active substance: GSK2251052 and [14C]-GSK2251052

Procedures: pain, licht bleeding, bruses, possible infection.

A single dose of GSK2251052 as an injection has been given to 32 healthy
volunteers and as a pill to 18 healthy volunteers. Multiple doses of
GSK2251052 have been given as an injection to 40 healthy volunteers and as a
pill to 9 healthy volunteers.
The most common reported side effects after single or multiple intravenous
doses of GSK2251052 were drop in blood pressure upon standing, diarrhea,
headache, sore chest muscles, feeling tired, abnormal heartbeat, dizziness and
nausea. There were also changes observed in some lab results including red
blood cells, reticulocytes (*young* red blood cells), and liver tests after
multiple doses of GSK2251052 were given. However, these changes were not
associated directly with signs or symptoms and lab results returned to normal
after dosing stopped. Your blood will be taken multiple times during this
study to look for this effect after your injected dose.