Infections, Human Immunodeficiency Virus and Tuberculosis Clinical Trial
Official title:
A Phase 1, Open Label, Placebo-Controlled Study to Evaluate the Effect of GSK1349572 on Iohexol and Para-Aminohippurate Clearance in Healthy Subjects
The current study is designed to confirm the mechanism behind the increase in serum creatinine observed during GSK1349572 therapy; specifically, the study will determine whether GSK1349572 has any effect on glomerular filtration rate (GFR) or effective renal plasma flow. Absent such effects, one may conclude that the small increases in serum creatinine observed are due to the inhibition of the tubular secretion of creatinine via organic cation transporter 2 (OCT2) consistent with in vitro data. .
GSK1349572 is an integrase inhibitor being developed for the treatment of human
immunodeficiency virus (HIV)-1 infection by GlaxoSmithKline (GSK) on behalf of Shionogi-ViiV
Healthcare LLC. In healthy subjects and in dose-ranging clinical trials of GSK1349572,
subjects showed a small, reversible increase in serum creatinine concentrations as compared
to the control groups; this occurred early during study drug administration and did not
progress over time. In vitro data demonstrate that GSK1349572 inhibits the organic cation
transporter (OCT2), which mediates the tubular secretion of creatinine; drugs such as
cimetidine with similar effects on OCT2 lead to a nonpathological increase in creatinine
with no effect on glomerular filtration rate (GFR). The current study is designed to confirm
the mechanism behind the increase in serum creatinine observed during GSK1349572 therapy;
specifically, the study will determine whether GSK1349572 has any effect on GFR or effective
renal plasma flow. Absent such effects, one may conclude that the small increases in serum
creatinine observed are due to the inhibition of the tubular secretion of creatinine via
OCT2.
Subjects will be given GSK1349572 50mg once daily, 50mg twice daily or placebo once daily
for 14 days. Changes in the subject's GFR will be measured through administration of iohexol
and effective renal plasma flow will be measured using Para-Aminohippurate (PAH) on days -1,
7 and 14. Changes in serum creatinine and other renal biomarkers will be evaluated at
baseline and at various time points throughout the study.
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Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment