A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: The ECLIPSE (Epanova® compared to Lovaza® in a pharmacokinetic single-dose evaluation) study

BACKGROUND: Omega-3 (OM-3) fatty acid products are indicated for the treatment of severe hypertriglyceridemia; however, the omega-3-acid ethyl ester (OM-3 EE) formulations require significant pancreatic lipase stimulation with high-fat meals for adequate intestinal absorption of the metabolites eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A novel omega-3 free fatty acid (OM-3 FFA) formulation (Epanova (R), Omthera Pharmaceuticals Inc., Princeton, NJ) was developed to maximize EPA and DHA bioavailability during a low-fat diet. OBJECTIVE: To compare the relative bioavailability of EPA and DHA from single 4-gram doses of OM-3 FFA and a prescription OM-3 EE (Lovaza (R), GlaxoSmithKline, Research Triangle Park, NC). METHODS: This was a randomized, open-label, single close, 4-way crossover, bioavailability study of OM-3 FFA and OM-3 EE administered during periods of low-fat and high-fat consumption to 54 overweight adults. Bioavailability was determined by the In-transformed area under the plasma concentration versus time curve (AUC(0-t)) during a 24-hour interval for EPA and DHA (baseline-adjusted). RESULTS: The baseline-adjusted AUC(0-t) for total EPA + DHA during the low-fa period was 4.0-fold greater with OM-3 FFA compared with OM-3 EE (2650.2 vs 662.0 nmol.h/mL, respectively; P < .0001). During the high-fat period, AUC(0-t) for OM-3 FFA was approximately 1.3-fold greater than OM-3 EE (P < .0001). During the low-fat period, 30 of 51(58.8%) subjects dosed with OM-3 FFA maintained an AUC(0-t) that was >= 50% of the respective high-fat AUC(0-t) in contrast to only 3 of 50 (6.0%) subjects dosed with OM-3 EE. CONCLUSIONS: During a low-fat consumption period, the OM-3 FFA formulation provided dramatically improved bioavailability over the OM-3 EE formulation in overweight subjects. These findings offer a potential therapeutic advantage of the OM-3 FFA formulation for the treatment of severe hypertriglyceridemia as these patients are expected to adhere to a low-fat diet. (C) 2012 National Lipid Association. All rights reserved.