This is a randomized, open-label crossover study. The primary objective of this study is to compare the relative bioavailability of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and the ethyl esters of EPA and DHA in plasma from a single 2 g or 4 g dose of Epanova® or 4 g Lovaza®.

Inclusion Criteria:

1. Male or female, ≥18 years of age;
2. History of serum TG concentration ≥500 mg/dL within the past 5 years;
3. Have at least one episode of documented hospitalization for pancreatitis due to hypertriglyceridemia in his/her lifetime;
4. Have no health conditions that would prevent him/her from fulfilling the study requirements as judged by the Investigator on the basis of physical examination, ECG, medical history, and routine laboratory test results;
5. Willing to maintain his/her current activity level and to follow either the NCEP TLC diet with a caloric target for weight maintenance or a prescribed low-fat diet during the screening, treatment, and washout periods (Visits 1 through 6b; Weeks -4 through 12);
6. Willing to eat the standardized breakfast, lunch, and dinner meals and snacks before and during Visits 4b and 6b (Weeks 4 and 12);
7. Willing to abstain from alcohol consumption and avoid vigorous physical activity for 48 hours prior to Visits 3 through 6b (Weeks 0 through 12); and
8. Subject understands the study procedures and is willing and able to sign the informed consent form to participate in the study and the Health Insurance Portability and Accountability Act authorization for release of relevant protected health information to the Investigators and study personnel.

Exclusion Criteria:

1. An allergy or intolerance to omega-3 fatty acids, omega-3-acid ethyl esters, fish, or any of the components of the standardized breakfast, lunch, or dinner meals or snacks (as described to them by study staff)
2. Poorly controlled hypertension (resting blood pressure ≥160 mmHg systolic and/or ≥100 mmHg diastolic) prior to randomization (Visit 3 [Week 0])
3. A history of cancer (other than basal cell carcinoma) in the last 2 years
4. A recent cardiovascular event (i.e., myocardial infarction, acute coronary syndrome, new onset angina, stroke, transient ischemic attack, unstable congestive heart failure requiring a change in treatment), aortic aneurysm or resection, carotid endarterectomy, or revascularization procedure within the 6 months prior to Visit 1