A 12-Week, Randomized, Double-Blind, Olive Oil-Controlled Phase 3
Study to Assess the Efficacy and Safety of EPANOVA* in Subjects With
Severe Hypertriglyceridemia

Epanova* is the name of the investigational study drug being tested to learn if
it may lower high triglycerides and contains omega 3 fatty acids. Triglycerides
are a type of fat found in your blood. When triglycerides are maintained at
low levels, they are healthy. However, they can cause health problems if the
levels become too high. High triglyceride levels can lead to increased risk of
developing heart disease.
There is evidence that omega-3 fatty acids may reduce the risk of heart disease
by lowering triglyceride levels.

Primary Objectives
The primary objectives of the study are:
· To determine the efficacy of Epanova 2 g daily compared to olive oil 2 g
daily for 12 weeks in lowering serum TG levels in subjects with severe
hypertriglyceridemia (TG levels *500 mg/dL [5.65 mMol/L] and <2500 mg/dL [28.25
mMol/L]) and
· To determine the safety and tolerability of Epanova.

This is a double-blind, randomized, olive oil-controlled study to investigate
the efficacy and safety of Epanova as an adjunct therapy to diet for reduction
of TG levels in subjects with severe hypertriglyceridemia. The study consists
of an approximately 8-week screening period
that includes a diet and lifestyle stabilization and washout period and a
12-week treatment period.
During the screening period and treatment period, all visits are to be within
±3 days of the scheduled time.
Screening Period
Visit 1 will occur at Week -8 for subjects requiring washout and/or statin,
cholesterol-absorption inhibitor (CAI), or statin-CAI stabilization. This
includes subjects who:
· Were previously on omega-3 drugs/supplements;
· Require adjustment to or addition of permitted statins, CAI, or statin-CAI
combination;
· Have not been on a permitted stable dose of statin, CAI, or statin-CAI
combination for at least 4 weeks prior to Visit 1; and/or
· Need to washout of bile acid sequestrants, fibrates, niacin, and other
supplements known to alter lipid metabolism.
For these subjects who require washout and/or statin, CAI, or statin-CAI
stabilization, at Visit 1 (Week -8) screening procedures will be performed.
Subjects will return at Visit 1a (Week -2) for their first qualifying lipid
measurement.

For subjects not requiring washout, Visit 1 will occur at Week -2. All
screening procedures will be performed at this visit including the first
qualifying lipid measurement.
At Visit 2 (Week -1), all subjects will return for their second lipid
qualifying measurement. If at Visit 2 the subject does not have an average TG
*500 mg/dL (5.65 mMol/L) and <2500 mg/dL (28.25 mMol/L), the TG measurement may
be repeated one additional time after Visit 2 (Visit 2a). The subject*s
qualifying measurement would be the average of Visit 1 or 1a + Visit 2 + Visit
2a (repeat measurement).

To be eligible for randomization, the subject must have a qualifying TG *500
mg/dL (5.65 mMol/L) and <2500 mg/dL (28.25 mMol/L). Of the total number of
subjects, approximately 50% will have a qualifying TG >885 mg/dL (10 mMol/L)
and <2500 mg/dL (28.25 mMol/L). Once approximately 50% of the total subjects
has been reached for each TG group, enrollment of subjects with that specific
TG criterion will stop. Subjects will be equally
allocated to each treatment group.
At the screening visit, all subjects will receive counseling regarding the
National Cholesterol Education Program Therapeutic Lifestyle Changes (TLC) diet
and will receive basic instructions on how to follow this diet. Treatment
Period At Visit 3 (Week 0), approximately 116 subjects will be randomized in a
1:1 ratio to receive daily olive oil 2 g or Epanova 2 g. Subjects will be
stratified to ensure a balanced allocation of subjects who are users and
non-users of lipid-altering drugs allowed at randomization. During the
treatment period, subjects will return to the site at Visit 4 (Week 6), Visit 5
(Week 10), and Visit 6 (Week 12) for efficacy and safety evaluations.

Eligible subjects will be randomly assigned at Visit 3 (Week 0) to receive
orally Epanova 2 g daily or olive oil 2 g daily. Epanova and olive oil will be
provided in 1 g polyacrylate-coated soft gel capsules. All capsules will be
taken once per day, without regard to meals, for 12 weeks. At clinic visits,
study drug will be administered at the clinic after fasting blood draws are
complete.

Epanova* has been administered in a total of 731 patients for 6-12 weeks. The
most common side effect (occurring in * 2% of patients treated with Epanova*
are: -gastrointestinal (GI) disorders (such as diarrhea, nausea, gas (belching
and/or flatulence), vomiting, abdominal pain, indigestion and irritable bowel),
feeling tired, bruising, increased blood sugar, increased blood lipids,
increased weight, diabetes, Joint and/or back pain, headache, an alteration in
the sense of taste, rash and high blood pressure.

In general on the clinical trials, Epanova* was well tolerated and most effects
were mild or moderate in severity and got better during the study.

It is hoped that the results of this study will help the sponsor learn which
treatments for hypertriglyceridemia are well tolerated and effective.

This study has two periods. A Screening/Washout/Diet Stabilization and a
Treatment period.

If the patient agrees to participate in this study:
* He/she will come in for approximately 6-8 visits at the study center. Each
study visit may take a maximum of 2 hours, but often they take less time.
* Fasting blood samples will be collected at least 6 times throughout the
study. A total of about 213 ml (12 tablespoons or a little more than 1/2 cup)
of blood will be collected.