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).

CONCLUSION:

TAK-085 produced a favorable shift in the LDL particle size in Japanese patients with hypertriglyceridemia. JAPIC Clinical Trials Information: Japic CTI-090937.

• Authors: Ichiro Tatsuno, Kentarou Kudou, Tomoya Kagawa
• Journal: Cardiovascular therapeutics (Cardiovasc Ther) Vol. 33 Issue 6 Pg. 317-23 (Dec 2015) ISSN: 1755-5922 [Electronic] England
• PMID: 26222126 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Cardiovascular Therapeutics published by John Wiley & Sons Ltd.

Chemical References

• APOB protein, human
• Apolipoprotein B-100
• Biomarkers
• Cholesterol, LDL
• Drug Combinations
• Hypolipidemic Agents
• TAK-085
• Docosahexaenoic Acids
• Eicosapentaenoic Acid

Topics

• Adult
• Aged
• Apolipoprotein B-100 (blood)
• Biomarkers (blood)
• Cholesterol, LDL (blood)
• Docosahexaenoic Acids (therapeutic use)
• Double-Blind Method
• Drug Combinations
• Eicosapentaenoic Acid (analogs & derivatives, therapeutic use)
• Female
• Humans
• Hypertriglyceridemia (blood, diagnosis, drug therapy)
• Hypolipidemic Agents (therapeutic use)
• Japan
• Male
• Middle Aged
• Particle Size
• Time Factors
• Treatment Outcome