Epanova® for Lowering Very High Triglycerides II (EVOLVE II)
Condition: Hypertriglyceridemia
MeSH terms: Hypertriglyceridemia
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      [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 (6 mmol/L) and <2500 mg/dL
      (28 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 (6 mmol/L)
      and <2500 mg/dL (28 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 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 (NCEP) Therapeutic Lifestyle Changes (TLC) diet and will
      receive basic instructions on how to follow this diet. See Appendix C.]

      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 by lipid-altering drugs to
      ensure a balanced allocation of subjects who are users and non-users of the following
      permitted lipid-altering drugs in each treatment group: statin, CAI, or statin-CAI
      combination. 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.
    

Intervention name(s): Epanova; Olive Oil
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Other intervention name(s): omega-3 free fatty acids; placebo comparator
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Hypertriglyceridemia; Dyslipidemia; Eicosapentaenoic acid; EPA; Docosahexaenoic acid; DHA