The objective of this study is to evaluate the effect of boceprevir (steady state) on the pharmacokinetics of a single dose of raltegravir. The effect on the boceprevir pharmacokinetics of a single dose raltegravir will also be evaluated (compared to historical controls). Furthermore, the safety profile of the combination is studied.
A considerable percentage of HIV infected patients is also infected with the hepatitis C virus (HCV). HIV/HCV co-infected patients are likely to simultaneously use treatment for their HIV infection as well as HCV treatment. Therefore, it is important to know if drug-drug interactions occur when combining those treatments. Raltegravir is an HIV integrase inhibitor and approved by the FDA in 2007. Boceprevir is a potent HCV NS3 serine protease inhibitor and is currently in Phase III clinical development. Combined use of boceprevir and raltegravir is not expected to give a major drug-drug interaction as raltegravir is not a CYP3A substrate and thus will not be affected by the strong inhibition of CYP3A by boceprevir. Raltegravir is metabolized by UGT but boceprevir is not known to influence UGT. However, recent data indicate that raltegravir is a P-gp substrate and boceprevir is a substrate and a moderate inhibitor of P-gp in vitro. Even when no drug interaction is expected, it may be recommended to collect sufficient evidence that this is the case as in many cases un-expected drug-drug interactions have been observed in the past. The current study is designed to evaluate the effect of steady state boceprevir on the pharmacokinetics of a single dose of raltegravir and the safety profile when used in combination. Furthermore the effect of a single dose raltegravir is studied on the pharmacokinetics of steady state boceprevir in comparison with historical controls.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
10 days of boceprevir 800mg TID
raltegravir 400mg single dose
CRCN
Nijmegen, Netherlands
raltegravir concentrations
To determine the effect of chronic use of boceprevir on the single-dose pharmacokinetics of raltegravir 400mg in healthy volunteers
Time frame: during 12hours on two occasions
adverse events
to determine the safety of a single dose of raltegravir 400mg when combined with chronic use of boceprevir
Time frame: entire study
boceprevir concentrations
To determine the effect of a single-dose pharmacokinetics of raltegravir 400mg on chronic use of boceprevir in healthy volunteers
Time frame: during 8 hours on one occasion; predose 4 times over a period of 10 days
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