GSK1349572 is an integrase inhibitor that is currently in Phase 2 clinical trials for the
treatment of HIV infection. As GSK1349572 development progresses, it may be dosed with
non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) including efavirenz (EFV,
Sustiva). Efavirenz is a known inducer of CYP3A4. GSK1349572 is primarily metabolized via
UGT1A1, however it also has a CYP component to its metabolism, thus a drug interaction
between GSK1349572 and EFV is likely. A previous study showed that another NNRTI, etravirine
which is also a known inducer of CYP3A and UGT, reduced GSK1349572 exposure significantly.
GSK1349572 is not an inhibitor or inducer of CYP3A and is not expected to have impact on
pharmacokinetics (PK) of EFV.
This study will investigate the dose proportionality between single doses of 50mg and 100mg
of GSK1349572 and will compare steady-state plasma PK, safety and tolerability of GSK1349572
50 mg every 24h (q24h) with and without efavirenz 600 mg q24h. Approximately 12 subjects will
receive a single dose of GSK1349572 100 mg (Treatment A) in Period 1 followed by a washout of
greater than or equal to 6 days. In Period 2 subjects will receive GSK1349572 50mg q24h for 5
days (Treatment B). Subjects will then be administered GSK1349572 50mg q24h in the morning in
combination with EFV 600 mg q24h (Treatment C) in the evening for 14 days in Period 3. There
will be no washout between Periods 2 and 3. Safety evaluations and serial PK samples for
GSK1349572 will be collected during each treatment period. A follow-up visit will occur 7-14
days after the last dose of study drug.
This study will be conducted at one center in the US, with healthy adult male and female
subjects.