GSK1349572 Hepatic Impairment Study

GSK1349572 is an integrase inhibitor that is currently in clinical development for the
treatment of human immunodeficiency virus (HIV) infection. GSK1349572 is metabolized
primarily by uridine diphosphate glucuronosyltransferase (UGT)1A1 with a minor role of
Cytochrome P450 (CYP)3A. Hepatic impairment could potentially alter the clearance and
plasma protein binding of GSK1349572. This study will evaluate the single dose
pharmacokinetics and safety of GSK1349572 in healthy subjects and in subjects with mild or
moderate hepatic impairment based on Child-Pugh category.

This is a single-dose, open-label, parallel group, two-part, adaptive study in adult males
and females with mild or moderate hepatic impairment and matched, healthy control subjects
with normal hepatic function. Healthy control subjects (16) will be matched for gender,
age, and BMI to the subjects in the mild (8) or moderate (8) hepatic impairment category.
In Part 1, approximately 8 subjects with moderate hepatic impairment (cohort 1) and 8
matched, control subjects (cohort 2) will each receive GSK1349572 50 mg as a single dose in
the fasted state followed by pharmacokinetic sampling for total concentrations of GSK1349572
in plasma. Free (unbound) plasma concentrations of GSK1349572 will also be evaluated at
sparse, selected time points. If the geometric mean total plasma area under the
concentration curve (AUC) of GSK1349572 is increased by > 2-fold in moderately impaired
subjects compared to matched controls, Part 2 will be conducted to evaluate GSK1349572
pharmacokinetics in another group of subjects with mild impairment (8, cohort 3) and
matched, control subjects (8, cohort 4). Vital signs, electrocardiograms (ECGs), and
adverse events will be monitored throughout the study. A follow-up visit will occur 7-10
days after the dose of study drug.