Severe Hypertriglyceridemia
Conditions
Keywords
dyslipidemia, hyperlipidemia, omega-3 carboxylic acid
Brief summary
The primary objective of the study is to determine the efficacy of Epanova (omefas) compared to placebo in lowering serum triglycerides in subjects with severe hypertriglyceridemia.
Interventions
DRUGplacebo
4 capsules (1g) daily for 12 weeks
DRUGomefas
2 capsules (1g) + 2 placebo daily for 12 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women, \>=18 years of age. * Very high serum TG values in the range \>=500 mg/dL and \<2000 mg/dL (\>=5.65 mmol/L and \<22.60 mmol/L)
Exclusion criteria
* Allergy or intolerance to omega-3 fatty acids, omega-3-acid ethyl esters, or fish. * Known lipoprotein lipase impairment or deficiency or apolipoprotein C-II deficiency or familial dysbetalipoproteinemia. * Unable to discontinue use of omega-3 drugs/supplements. * 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. * Women who are pregnant, lactating, or planning to become pregnant. Women of childbearing potential who are not using acceptable contraceptive methods. * Use of tamoxifen, estrogens or progestins that has not been stable for \>4 weeks prior to Visit 1. * Use of oral or injected corticosteroids or anabolic steroids. * History of pancreatitis. * History of symptomatic gallstone disease, unless treated with cholecystectomy. * Uncontrolled diabetes. * Uncontrolled hypothyroidism or thyroid stimulating hormone (TSH). * History of cancer (other than basal cell carcinoma) in the past 2 years. * Cardiovascular event (i.e., myocardial infarction, acute coronary syndrome, new onset angina, stroke, transient ischemic attack, unstable congestive heart failure requiring a change in treatment) or revascularization procedure within six months prior to Visit 1. * Use of anticoagulants (e.g. warfarin \[Coumadin®\], coumarin, heparin, enoxaparin, clopidogrel). * Presence of an aortic aneurysm or resection of an aortic aneurysm within six months prior to Visit 1. * Recent history (within six months prior to Visit 1) or current significant nephrotic syndrome, pulmonary, hepatic, biliary, gastrointestinal or immunologic disease. * Poorly controlled hypertension. * Any of the following laboratory criteria: serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), glucose, glomerular filtration rate (GFR), platelet count,or hemoglobin outside of study range. * Recent history (past 12 months) of drug abuse or alcohol abuse. * Exposure to any investigational product, within 4 weeks prior to Visit 1. * Presence of 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Serum Triglycerides | 12 weeks | The primary endpoints are the differences in mean percent changes from baseline to end-of-treatment in triglycerides between placebo and the 2g/day, 3g/day and 4g/day Epanova groups |
Countries
Denmark, Hungary, India, Netherlands, Russia, Ukraine, United States
Participant flow
Recruitment details
The enrollment period started April 2011 and the last subject visit was February 2012. All subjects were qualified at the clinical site and eligibility was determined by each PI (74 US and International clinical sites).
Pre-assignment details
Subjects who needed to washout omega-3 drugs/supplements or adjust or add a permitted statin, CAI or combination had an 8-week screening. All other subjects, including those on a stable statin, CAI or statin-CAI, or who needed to washout of bile acid sequestrants, fibrates, niacin and other lipid altering supplements had a 4-week screening period.
Participants by arm
| Arm | Count |
|---|---|
| Olive Oil (Placebo) placebo : 4 capsules (1g) daily for 12 weeks | 99 |
| Epanova 2 g omefas : 2 capsules (1g) + 2 placebo daily for 12 weeks | 100 |
| Epanova 3 g omefas : 3 capsules (1g) + 1 placebo daily for 12 weeks | 101 |
| Epanova 4 g omefas : 4 capsules (1g)daily for 12 weeks | 99 |
| Total | 399 |
Baseline characteristics
| Characteristic | Olive Oil (Placebo) | Epanova 2 g | Epanova 3 g | Epanova 4 g | Total |
|---|---|---|---|---|---|
| Age, Continuous | 50.8 Years STANDARD_DEVIATION 10.59 | 51.1 Years STANDARD_DEVIATION 9.79 | 51.2 Years STANDARD_DEVIATION 8.75 | 52.9 Years STANDARD_DEVIATION 10.92 | 51.5 Years STANDARD_DEVIATION 10.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 8 Participants | 4 Participants | 7 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 92 Participants | 97 Participants | 92 Participants | 374 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 22 Participants | 20 Participants | 22 Participants | 28 Participants | 92 Participants |
| Sex: Female, Male Male | 77 Participants | 80 Participants | 79 Participants | 71 Participants | 307 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 99 | 23 / 100 | 18 / 101 | 16 / 99 |
| serious Total, serious adverse events | 2 / 99 | 1 / 100 | 4 / 101 | 0 / 99 |
Outcome results
Primary
Fasting Serum Triglycerides
The primary endpoints are the differences in mean percent changes from baseline to end-of-treatment in triglycerides between placebo and the 2g/day, 3g/day and 4g/day Epanova groups
Time frame: 12 weeks
Population: The Intent-to-Treat (ITT) Population was comprised of all subjects who were randomized. In the event that randomized subjects terminated before treatment or had no post-treatment efficacy assessments, a modified ITT Population was implemented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Olive Oil (Placebo) | Fasting Serum Triglycerides | -4.26 Percent change from baseline |
| Epanova 2 g | Fasting Serum Triglycerides | -25.94 Percent change from baseline |
| Epanova 3 g | Fasting Serum Triglycerides | -25.46 Percent change from baseline |
| Epanova 4 g | Fasting Serum Triglycerides | -30.86 Percent change from baseline |
p-value: 0.00595% CI: [-40.7, -2.89]ANCOVA p-value on ranked data
p-value: 0.00795% CI: [-40.32, -2.29]ANCOVA p-value on ranked data
p-value: <0.00195% CI: [-45.12, -8.38]ANCOVA p-value on ranked data