Epanova® for Lowering Very High Triglycerides II (EVOLVE II)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||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 (EVOLVE II)|
- Triglyceride (TG) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]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 [6 mMol/L] and <2500 mg/dL [28 mMol/L]).
- TG lowering in subgroup of subjects with high baseline levels [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]To determine the effect of Epanova 2 g daily compared to olive oil 2 g daily for 12 weeks in lowering serum TG levels in subjects with at least 1 qualifying TG >885 mg/dL (10 mMol/L) and <2500 mg/dL (28 mMol/L).
- TG lowering in subgroup of subjects with Fredrickson Type V hyperlipidemia [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]To determine the effects of Epanova 2 g daily compared to olive oil 2 g daily for 12 weeks in lowering TG levels in subjects with Fredrickson Type V hyperlipidemia (TG/VLDL-C ≥6).
- Non-high-density lipoprotein cholesterol (non-HDL-C) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]The percent change in non-HDL-C from baseline to Week 12 endpoint.
- High-density lipoprotein cholesterol (HDL-C) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]The percent change in HDL-C from baseline to Week 12 endpoint.
|Study Start Date:||December 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: Epanova 2 g/day
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.
Other Name: omega-3 free fatty acids
Placebo Comparator: Olive Oil 2 g/day
Drug: Olive Oil
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 Name: placebo comparator
[During the screening period and treatment period, all visits are to be within ±3 days of the scheduled time.]
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.]
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.
|Contact: Douglas Kling||(908) email@example.com|
|Contact: Judith Johnson||(908) firstname.lastname@example.org|
|United States, Oklahoma|
|COR Clinical Research, LLC.||Recruiting|
|Oklahoma City, Oklahoma, United States, 73103|
|Contact: Clinton N Corder, MD 405-272-8481|
|Principal Investigator: Clinton N Corder, MD|
|Study Director:||Michael H Davidson, MD, FACC||Omthera Pharmaceuticals, Inc|