No clinically relevant drug–drug interactions when dalcetrapib is co-administered with atorvastatin

Abstract

Objectives: Dalcetrapib, which targets cholesteryl ester transfer protein, is in clinical development for prevention of cardiovascular events and is likely to be used concomitantly with statins. Two studies investigated co-administration of dalcetrapib with atorvastatin and any effects of the timing of atorvastatin on the pharmacokinetics of dalcetrapib.

Research design and methods: Two crossover studies were performed in healthy subjects: a two-period study of dalcetrapib 900 mg concurrently with atorvastatin (concurrent dosing study) and a three-period study of dalcetrapib 600 mg (dose chosen for Phase III) with atorvastatin concurrently or serially 4 h after dalcetrapib (interval dosing study).

Main outcome measures: The primary pharmacokinetic end points were AUC_{0 – 24} and C_max; lipid effects and tolerability were secondary end points.

Results: In the concurrent study (n = 26), co-administration reduced dalcetrapib AUC_{0 – 24} and C_max and caused small changes in AUC_{0 – 24} and C_max of atorvastatin and its active metabolites. In the interval study (n = 52), serial and concurrent co-administration of atorvastatin resulted in similar reductions in dalcetrapib exposure that were comparable to those observed in the concurrent dosing study. Co-administration did not decrease the efficacy of dalcetrapib or atorvastatin and was generally well tolerated.

Conclusions: These results indicate no clinically relevant interactions for co-administration of dalcetrapib with atorvastatin.

Keywords::

• atorvastatin
• CETP
• dalcetrapib
• drug–drug interactions

Acknowledgements

Content has previously been presented as an abstract and poster at the National Lipid Association Annual Scientific Sessions in Miami, Florida, 30 April to 3 May 2009. Editorial assistance was provided by K Whitfield, Prime Healthcare Ltd.

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