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.