This is a dose escalation/dose finding, double-blind, placebo-controlled, parallel study of
GSK2126458 in subjects with IPF. The study is designed to explore a number of doses of
GSK2126458 for engagement of pharmacology after short term dosing. It is anticipated that
approximately 24 subjects will be enrolled in this study. Actual number of cohorts in this
study could vary up to a maximum of 6 cohorts (n=4/cohort; 3 on active and 1 on placebo).
Each cohort will consist of four subjects who will be randomised to receive GSK2126458 (three
subjects) or placebo (one subject) for approximately 8 days (7 to 10 days). On Day 1 they
will receive their first dose of GSK2126458 (or placebo) and safety, tolerability and PK/PD
in the blood will be measured for up to 8 hours post-dose. Subjects will then be discharged
from the site with study drug until the last day of dosing. They will also receive hand held
spirometers and instructions on action to be taken in case of deterioration in pulmonary
function or any other adverse events (AEs). On the last day of dosing they will return to the
site for a repeat of the Day 1 procedures.
A bronchoalveolar lavage (BAL) and [18F]-fluoro-deoxyglucose (FDG)- positron emission
tomography / computed tomography (PET/CT) scan will be conducted twice during the study;
once, at least 2 days before dosing commences and again during the course of the dosing
After the final subject in each cohort has completed dosing, a dose escalation meeting will
take place. Safety and tolerability and PK data will be reviewed during this meeting and
decisions made may include but are not limited to: escalate the dose, decrease the dose or
repeat the same dose in the next cohort; stop the study.