title: Effect of TAK-085 on Low-density Lipoprotein Particle Size in Patients with Hypertriglyceridemia: A Double-blind Randomized Clinical Study.
abstract: 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).
  
  
  CONCLUSIONS
  TAK-085 produced a favorable shift in the LDL particle size in Japanese patients with hypertriglyceridemia. JAPIC Clinical Trials Information: Japic CTI-090937.
authors.affiliation: Center of Diabetes, Endocrine and Metabolism, School of Medicine, Sakura Hospital, Toho University, Chiba, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.affiliation: Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Kentarou
authors.initials: K
authors.lastname: Kudou
authors.affiliation: Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kagawa
mesh_terms: D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D015415:Biomarkers; D008078:Cholesterol, LDL; D004338:Drug Combinations; D000960:Hypolipidemic Agents; C587319:TAK-085; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Large buoyant low-density lipoprotein; Low-density lipoprotein particle size; Small dense low-density lipoprotein