The study will determine the effect of 400 mg once daily of ketoconazole at steady state on
the pharmacokinetics of a single oral dose of GSK239512 in young healthy volunteers.
Ketoconazole is a strong inhibitor of CYP3A4, which is involved in metabolism of drugs. A
two-cohort design will be applied with cohort 1 aimed at providing a first estimate of the
interaction potential of GSK239512 and ketoconazole in terms of pharmacokinetic parameters in
a small number of subjects. Data from Cohort 1 will inform the decision of which dose to use
in Cohort 2, in which a larger number of subjects will be exposed to GSK239512 without and
with ketoconazole. The target maximum exposure is aimed to be similar to the exposure by a
single dose of 80 mcg of GSK239512 without CYP3A4 inhibition. In summary, the results from
this study will help to estimate the maximum increase in exposure of GSK239512 during
concomitant use of strong CYP3A4 inhibitors and will help define the subsequent dosing
strategy around GSK239512 and co-medications with potential to inhibit CYP3A4.