Effect of TAK‐085 on Low‐density Lipoprotein Particle Size in Patients with Hypertriglyceridemia: A Double‐blind Randomized Clinical Study

BACKGROUND: Low‐density lipoproteins (LDLs) comprise a heterogeneous group of particles with various size and density. A shift to larger LDL particle size is mainly the result of a decrease in small dense LDL (sd‐LDL) levels and an increase in large buoyant LDL (lb‐LDL) levels. METHODS: In a randomized, double‐blind study of TAK‐085 (containing docosahexaenoic and eicosapentaenoic acid‐ethyl esters [EPA‐E]) and an EPA‐E product in Japanese patients with hypertriglyceridemia, exploratory evaluations of the effects of the LDL particle size were performed on the basis of LDL‐cholesterol/apolipoprotein B ratios and LDL subfractions, which were analyzed with a polyacrylamide gel electrophoresis system. RESULTS: Patients were randomized to 12‐week treatment with TAK‐085 4 g/day (N = 210), TAK‐085 2 g/day (N = 205), or EPA‐E 1.8 g/day (N = 195). Treatment with TAK‐085 4 g/day, TAK‐085 2 g/day, and EPA‐E 1.8 g/day caused an increase in the LDL cholesterol/apolipoprotein B ratios (3.99%, 3.35%, and 0.66%, respectively), the mean diameter of LDL particles (1.12%, 0.84%, and 0.67%, respectively), and the level of lb‐LDL at the end of the study (16.37%, 9.51%, and 7.31%, respectively). The increases in the LDL cholesterol/apolipoprotein B ratios and the mean diameter of LDL particles from baseline to the end of the study were greater with TAK‐085 4 g/day than EPA‐E 1.8 g/day. TAK‐085 4 g/day and TAK‐085 2 g/day caused a decrease in the sd‐LDL levels (−16.21% and −6.96%, respectively). CONCLUSION: TAK‐085 produced a favorable shift in the LDL particle size in Japanese patients with hypertriglyceridemia. JAPIC Clinical Trials Information: Japic CTI‐090937.