Clinical trial NCT01408303: [E]PANOVA Combined With a [S]TATIN in [P]ATIENTS With HYPERT[R]IGLYCER[I]DEMIA to Reduce Non-HDL CHOLES[T]EROL
Official title: A 6-Week, Randomized, Double-Blind, Placebo(Olive Oil)-Controlled Study to Assess the Efficacy and Safety of Add-On Epanova® to Statin Therapy in Subjects With Persistent Hypertriglyceridemia and High Risk for Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertriglyceridemia
Cardiovascular Disease
Keywords: dyslipidemia
hyperlipidemia
cardiovascular risk
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Omthera Pharmaceuticals, Inc
name: Medpace, Inc.
First posted: 2011-08-03
Enrollment: 646
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to evaluate the efficacy of adding Epanova (2 g or 4 g daily) to an optimal statin monotherapy for lowering non-high-density lipoprotein (non-HDL) cholesterol in subjects with persistent hypertriglyceridemia and high risk for cardiovascular disease.

Detailed description: The primary efficacy variable is serum non-HDL cholesterol. The primary endpoints are the differences in mean percent changes from baseline to end-of-treatment in non-HDL cholesterol between placebo and the 2g/day and 4g/day Epanova groups. Baseline is defined as the average of Visits 2, 3 and 4 (Weeks -2, -1 and 0) and end-of-treatment is the average of Visits 5 and 6 (Weeks 5 and 6).

Eligibility criteria: Inclusion Criteria:

1. Men or women, ≥18 years of age.
2. Fasting triglyceride (TG) level ≥200 mg/dL and \<500 mg/dL.
3. The subject is a high risk for a future cardiovascular event.
4. The subject is treated with a statin and at or near LDL-C goal.

Exclusion Criteria:

1. Allergy or intolerance to omega-3 fatty acids and omega-3-acid ethyl esters.
2. Use of fibrates, bile acid sequestrants, or niacin or its analogues (greater than 200 mg/d) during screening.
3. Use of simvastatin 80 mg or Vytorin10/80 mg during screening.
4. Use of any eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) products.
5. Use of any supplement for the purpose of lowering plasma cholesterol during screening.
6. Use of weight loss drugs or programs during screening.
7. Use of erythromycin, telithromycin, clarithromycin, cyclosporine, itraconazole, ketoconazole, protease inhibitors, or nefazodone during screening.
8. Use of anticoagulants during screening.
9. Use of oral or injected corticosteroids during screening.
10. Use of tamoxifen, estrogens, progestins, or testosterone, that has not been stable for \>4 weeks at Visit 1, or is unstable during screening.
11. Use of \>750 mL/d grapefruit juice during screening.
12. Known lipoprotein lipase impairment or deficiency, or apolipoprotein C-II deficiency or familial dysbetalipoproteinemia.
13. History of pancreatitis.
14. Type I diabetes mellitus, use of insulin, or HbA1c \>10% at Visit 1.
15. Poorly controlled hypertension
16. Uncontrolled hypothyroidism, or thyroid stimulating hormone (TSH) \>1.5xULN at Visit 2.
17. Recent history or current significant nephrotic syndrome, pulmonary, hepatic, biliary, gastrointestinal or immunologic disease.
18. History of cancer (except non-melanoma skin cancer, or carcinoma in situ of cervix) within the previous two years.
19. Females who are pregnant, planning to be pregnant during the study period, lactating, or women of childbearing potential who are not using an acceptable method of contraception.
20. Creatine kinase \>5.0 times upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2.5 times ULN at Visit 2.
21. Current or recent history (past 12 months) of drug or alcohol abuse.
22. Exposure to any investigational agent within 4 weeks prior to Visit 1.
23. Any other condition the investigator believes would interfere with the subject's ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the subject at undue risk.

Primary outcomes:
measure: Serum Non-HDL Cholesterol
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Encinitas
country: United States
state: California
city: Lomita
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Spring Valley
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Brandon
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Melbourne
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Oviedo
country: United States
state: Florida
city: Ponte Vedra
country: United States
state: Florida
city: St. Petersburg
country: United States
state: Florida
city: Addison
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Oakbrook Terrace
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Newton
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Madisonville
country: United States
state: Kentucky
city: Auburn
country: United States
state: Maine
city: Oxon Hill
country: United States
state: Maryland
city: Troy
country: United States
state: Michigan
city: Edina
country: United States
state: Minnesota
city: Chesterfield
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Butte
country: United States
state: Montana
city: Las Vegas
country: United States
state: Nevada
city: Berlin
country: United States
state: New Jersey
city: Endwell
country: United States
state: New York
city: New Windsor
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Cary
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: High Point
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Lyndhurst
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Eugene
country: United States
state: Oregon
city: Harleysville
country: United States
state: Pennsylvania
city: Jersey Shore
country: United States
state: Pennsylvania
city: Lansdale
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Mount Pleasant
country: United States
state: South Carolina
city: Mt Pleasant
country: United States
state: South Carolina
city: Rapid City
country: United States
state: South Dakota
city: Bristol
country: United States
state: Tennessee
city: Gray
country: United States
state: Tennessee
city: Kingsport
country: United States
state: Tennessee
city: Corpus Christi
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Katy
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Murray
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Olympia
country: United States
state: Washington
Study officials:
affiliation: Omthera Pharmaceuticals, Inc
name: Michael H Davidson, MD, FACC
role: STUDY_DIRECTOR
References:
citation: Dunbar RL, Nicholls SJ, Maki KC, Roth EM, Orloff DG, Curcio D, Johnson J, Kling D, Davidson MH. Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: a randomized, controlled, double-blind trial. Lipids Health Dis. 2015 Sep 2;14:98. doi: 10.1186/s12944-015-0100-8.
citation: Maki KC, Orloff DG, Nicholls SJ, Dunbar RL, Roth EM, Curcio D, Johnson J, Kling D, Davidson MH. A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial). Clin Ther. 2013 Sep;35(9):1400-11.e1-3. doi: 10.1016/j.clinthera.2013.07.420. Epub 2013 Aug 30.