NEW YORK (Reuters Health) – An investigational drug AMR101 containing purified eicosapentaenoic acid and no docosahexaenoic acid reduces very high triglyceride levels by up to 45% compared to placebo, and does not cause an increase in LDL levels, according to the results of a double-blind randomized trial.
The findings appear in the American Journal of Cardiology online June 20. Preliminary results were released in November.
In their paper, Dr. Harold E. Bays, with the Louisville Metabolic and Atherosclerosis Research Center, Kentucky, and colleagues explain that fibrates and fish oil agents used to lower triglycerides often increase LDL cholesterol substantially. However, some small studies indicated that this effect was not seen if patients were given eicosapentaenoic acid (EPA) without docosahexaenoic acid (DHA).
The current trial tested the effect of AMR11360, which is at least 96% EPA ethyl ester with no DHA, in 229 patients with fasting triglyceride levels between 500 and 2000 mg/dL. Participants received 2 g/day or 4 g/day of AMR101 or placebo over 12 weeks, with a 40-week open-label extension on 4 g/day.
After 12 weeks, median triglyceride levels had dropped from 679.5 to 502.0 mg/dL in the 4-g/day group, from 656.5 to 605.5 mg/dL in the 2-g/day group, and increased from 703.0 to 745.5 mg/dL in the placebo group. This translates to a placebo-corrected decrease in triglyceride in the two active treatment groups of 33.1% (p<0.0001) and 19.7% (p=0.0051), respectively.
Among patients with triglyceride levels above 750 mg/dL, corresponding decreases with the two dosages were 45.4% and 32.9%, the report indicates.
Median placebo-corrected LDL cholesterol actually decreased slightly with 4 g/day AMR101 (-2.3%) and increased slightly with the 2-g/day dose (5.2%), but neither change was statistically significant, the team found.
Treatment-emergent adverse events were generally mild or moderate, and rates were similar at 34% to 37% across the three treatment groups. “The most common treatment-emergent adverse events were gastrointestinal (i.e., diarrhea, nausea, and eructation), with the greatest numerical incidence in the placebo group,” the authors note.
Furthermore, an exploratory investigation of other lipid parameters showed that AMR101 significantly reduced non–HDL cholesterol, apolipoprotein B, lipoprotein-associated phospholipase A2, very low-density lipoprotein cholesterol, and total cholesterol.
“The results of the present study have demonstrated that in patients with very high TG (triglyceride) levels, AMR101 is the first non-statin TG-lowering therapy to reduce TG levels without significantly increasing the LDL cholesterol levels,” Dr. Bays and colleagues conclude.
They note that another trial has evaluated the effect of AMR101 in patients with elevated triglyceride levels of 200 to 500 mg/dL.
The current study was sponsored and designed by Amarin Pharma Inc., Mystic, Connecticut.
Reference:
Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Patients With Very High Triglyceride Levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] Trial)
Am J Cardiol 2011.
