Phase 0 study of the inhibition of cholesteryl ester transfer protein activity by JNJ-28545595 in plasma from normolipidemic and dyslipidemic humans.

Objective: To assess and validate the application of a non-radioactive assay for cholesteryl ester transfer protein (CETP) activity in clinical samples.

Design And Methods: In this Phase 0 study, CETP activity was measured following addition of the CETP inhibitor JNJ-28545595 to plasma samples from normolipidemic and three subgroups of dyslipidemic subjects with differing lipid profiles.

Results: CETP activity was elevated in plasma samples from dyslipidemic subjects compared to normolipidemic subjects. Increased triglyceride levels correlated with decreased CETP inhibition. The assay was found to have good analytical precision and high throughput potential as required for clinical trial sample analysis.

Conclusions: The results demonstrate that pharmacological inhibition of CETP is affected by the dyslipidemic nature of plasma samples. In addition, since the optimal degree of CETP inhibition for maximal cardiovascular benefit in patients is not known, this assay may be used to help define optimal dosing of CETP inhibitors.