Epanova® for Lowering Very High Triglycerides II (EVOLVE II)
Condition: Hypertriglyceridemia
MeSH terms: Hypertriglyceridemia
Intervention: Epanova; Olive Oil
Intervention description: Epanova will be provided in 1 g polyacrylate-coated soft gel capsules. Two 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.; Olive oil will be provided in 1 g polyacrylate-coated soft gel capsules. Two 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 379.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Hypertriglyceridemia; Dyslipidemia; Eicosapentaenoic acid; EPA; Docosahexaenoic acid; DHA

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Understanding of the study procedures, willingness to adhere to the study schedule,
             and agreement to participate in the study by giving written informed consent prior to
             screening;

          2. Willing to use an appropriate and effective method of contraception;

          3. Qualifying (average of Visit 1 or 1a + Visit 2 + Visit 2a [repeat measurement]) serum
             TG ≥500 mg/dL (6 mMol/L) and <2500 mg/dL (28 mMol/L);

          4. Body mass index ≥20 kg/m2;

          5. Untreated dyslipidemia or dyslipidemia treated with a statin, CAI, or statin-CAI
             combination that has been stable for 6 weeks prior to randomization; and

          6. Willingness to maintain current physical activity level and follow the TLC diet
             throughout the study.

        Exclusion Criteria:

          1. Allergy or intolerance to omega-3 fatty acids, omega-3-acid ethyl esters, or fish;

          2. Known lipoprotein lipase impairment;

          3. Known non-responder to omega-3 or fenofibrate therapy;

          4. Use of any prescription medications containing EPA and/or DHA (eg, Lovaza® or
             Vascepa®) within 8 weeks prior to randomization. Up to 1 g capsule/day of an omega-3
             dietary supplement will be permitted;

          5. Unable to discontinue use of bile acid sequestrants, fibrates or niacin (other than
             niacin-containing vitamins <200 mg), or any supplement used to alter lipid metabolism
             including but not limited to dietary fiber supplements, red rice yeast supplements,
             garlic supplements, soy isoflavone supplements, sterol/stanol products, or
             policosanols at screening;

          6. Use of tamoxifen, estrogens, or progestins that has not been stable for >4 weeks at
             screening or is unstable prior to randomization;

          7. Use of oral or injected corticosteroids or anabolic steroids prior to randomization;

          8. History of hospitalization for pancreatitis in the last 5 years;

          9. Uncontrolled diabetes (hemoglobin A1c [HbA1c] >10%);

         10. Uncontrolled hypothyroidism or thyroid-stimulating hormone (TSH) >5 mIU/L;

         11. History of cancer (other than basal cell carcinoma) in the past 2 years;

         12. Cardiovascular event (ie, myocardial infarction, acute coronary syndrome, new onset
             angina, stroke, transient heart attack, unstable congestive heart failure requiring a
             change in treatment), revascularization procedure or vascular surgery within 6 months
             of randomization;

         13. Use of simvastatin 80 mg or Vytorin 10/80 mg;

         14. Recent history (within 6 months of randomization) of significant nephrotic syndrome,
             pulmonary, hepatic, biliary, gastrointestinal, or immunologic disease;

         15. Poorly controlled hypertension (systolic blood pressure ≥180 mmHg and/or diastolic
             blood pressure ≥110 mmHg);

         16. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper
             limit of normal (ULN); if ALT/AST is >3 × ULN, the levels have been stable for 3
             months and are <5 × ULN;

         17. Exposure to any investigational product within 4 weeks of randomization; or

         18. Any condition or therapy which, in the opinion of the Investigator, might pose a risk
             to the subject or make participation in the study not in the subject's best interest.