Hypertriglyceridemia
Conditions
Keywords
hypertriglyceridemia, omega-3 fatty acids, statin, triglycerides, lipids, EPA, docosahexaenoic acid, fish, fatty acids, fibrates, niacin, lipid, atorvastatin, Lovaza, simvastatin, lovastatin, pravastatin, fluvastatin, rosuvastatin, Trilipix, Vytorin, Simcor, ezetimibe, Zetia, ethyl-EPA, ethyl icosapentate, Crestor, Zocor, Lipitor, Niaspan, LDL, HDL, cholesterol, dyslipidemia, VASCEPA, icosapent ethyl
Brief summary
The primary objective is to determine the efficacy of AMR101 (ethyl icosapentate) compared to placebo in lowering fasting triglyceride levels in patients with very high fasting triglyceride levels ≥ 500 and ≤ 2000 mg/dL.
Interventions
AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)
AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)
DRUGPlacebo
Placebo 4 capsules/day for 12 weeks (Weeks 1-12)
Sponsors
Amarin Pharma Inc.
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 and women, ages \>18 * Fasting triglyceride ≥500 mg/dL and ≤2000 mg/dL * Provide written informed consent and authorization for protected health information disclosure
Exclusion criteria
* Women who are pregnant or lactating, or planning to become pregnant * Use of non-statin lipid-altering drugs which cannot be stopped including fibrates, niacin, fish oil and other products containing omega-3 fatty acids or other dietary supplements with potential lipid-altering effects * History of pancreatitis * History of bariatric surgery or currently on weight loss drugs * Uncontrolled hypertension (BP \> 160/100) * HIV infection or on treatment with HIV-protease inhibitors, cyclophosphamide,or isotretinoin * Consumption of more than 2 alcoholic beverages per day * History of cancers (except if been disease free for \>5 years OR history was basal or squamous cell skin cancer) * Participation in another clinical trial involving an investigational agent in the last 30 days * Other parameters will be assessed at the study center to ensure eligibility for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Triglyceride Lowering Effect | baseline and 12 weeks | Median percent change from baseline to Week 12 in fasting serum triglyceride levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Very Low-density Lipoprotein Cholesterol Levels | baseline and 12 weeks | Median percent change from baseline to Week 12 in serum very low-density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day |
| Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Lipoprotein-associated Phospholipase A2 Levels | baseline and 12 weeks | Median percent change from baseline to Week 12 in serum Lipoprotein-associated Phospholipase A2 levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day |
| Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Group in Apolipoprotein B Levels | baseline and 12 weeks | Median in percent change from baseline to Week 12 in serum Apolipoprotein B levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day |
Other
| Measure | Time frame | Description |
|---|---|---|
| Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Low-density Lipoprotein Cholesterol Levels | baseline and 12 weeks | Median percent change from baseline to Week 12 in serum low density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day |
| Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Non-High-Density Lipoprotein Cholesterol Levels | baseline and 12 weeks | Median percent change from baseline to Week 12 in serum non-high density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day |
Countries
Denmark, Finland, Germany, India, Italy, Mexico, Netherlands, Russia, South Africa, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12) | 76 |
| AMR101 (Ethyl Icosapentate) - 2 g/Day AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12) | 76 |
| AMR101 (Ethyl Icosapentate) - 4 g/Day AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12) | 77 |
| Total | 229 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Triglycerides >2000 mg/dL | 1 | 0 | 1 |
| Overall Study | Withdrew Consent | 1 | 4 | 2 |
Baseline characteristics
| Characteristic | Placebo | AMR101 (Ethyl Icosapentate) - 2 g/Day | AMR101 (Ethyl Icosapentate) - 4 g/Day | Total |
|---|---|---|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 8.34 | 53.4 years STANDARD_DEVIATION 9.34 | 51.9 years STANDARD_DEVIATION 10.27 | 52.9 years STANDARD_DEVIATION 9.34 |
| Race/Ethnicity, Customized Other | 8 participants | 9 participants | 10 participants | 27 participants |
| Race/Ethnicity, Customized White | 68 participants | 67 participants | 67 participants | 202 participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 18 Participants | 54 Participants |
| Sex: Female, Male Male | 58 Participants | 58 Participants | 59 Participants | 175 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 76 | 10 / 76 | 2 / 77 |
| serious Total, serious adverse events | 0 / 76 | 1 / 76 | 1 / 77 |
Outcome results
Primary
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Triglyceride Lowering Effect
Median percent change from baseline to Week 12 in fasting serum triglyceride levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day
Time frame: baseline and 12 weeks
Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMR101 (Ethyl Icosapentate) - 2 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Triglyceride Lowering Effect | -7.0 Percent change from baseline |
| AMR101 (Ethyl Icosapentate) - 4 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Triglyceride Lowering Effect | -26.6 Percent change from baseline |
| Placebo | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Triglyceride Lowering Effect | 9.7 Percent change from baseline |
Comparison: A standard deviation of 45% in the TG measurements and a significance level of P \< 0.01 required a sample size of 69 completed patients per treatment group to provide greater than or equal to 90% power to detect a difference of 30% between AMR101 and placebo in the percentage of change from baseline in the fasting TG levels.p-value: <0.000195% CI: [-46.6, -21.5]Wilcoxon rank-sum test
p-value: 0.005195% CI: [-33.3, -5.6]Wilcoxon rank-sum test
Secondary
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Group in Apolipoprotein B Levels
Median in percent change from baseline to Week 12 in serum Apolipoprotein B levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day
Time frame: baseline and 12 weeks
Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMR101 (Ethyl Icosapentate) - 2 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Group in Apolipoprotein B Levels | 2.1 Percent change from baseline |
| AMR101 (Ethyl Icosapentate) - 4 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Group in Apolipoprotein B Levels | -3.8 Percent change from baseline |
| Placebo | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Group in Apolipoprotein B Levels | 4.3 Percent change from baseline |
p-value: 0.001995% CI: [-13.5, -3.2]Wilcoxon rank-sum test
p-value: 0.236795% CI: [-7.8, 1.9]Wilcoxon rank-sum test
Secondary
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Lipoprotein-associated Phospholipase A2 Levels
Median percent change from baseline to Week 12 in serum Lipoprotein-associated Phospholipase A2 levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day
Time frame: baseline and 12 weeks
Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMR101 (Ethyl Icosapentate) - 2 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Lipoprotein-associated Phospholipase A2 Levels | -5.1 Percent change from baseline |
| AMR101 (Ethyl Icosapentate) - 4 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Lipoprotein-associated Phospholipase A2 Levels | -17.1 Percent change from baseline |
| Placebo | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Lipoprotein-associated Phospholipase A2 Levels | -2.4 Percent change from baseline |
p-value: 0.000695% CI: [-20.2, -6.3]Wilcoxon rank-sum test
p-value: 0.236795% CI: [-12.3, 2.2]Wilcoxon rank-sum test
Secondary
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Very Low-density Lipoprotein Cholesterol Levels
Median percent change from baseline to Week 12 in serum very low-density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day
Time frame: baseline and 12 weeks
Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMR101 (Ethyl Icosapentate) - 2 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Very Low-density Lipoprotein Cholesterol Levels | 0.0 Percent change from baseline |
| AMR101 (Ethyl Icosapentate) - 4 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Very Low-density Lipoprotein Cholesterol Levels | -19.5 Percent change from baseline |
| Placebo | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Very Low-density Lipoprotein Cholesterol Levels | 13.7 Percent change from baseline |
p-value: 0.000595% CI: [-43.4, -13.9]Wilcoxon rank-sum test
p-value: 0.115295% CI: [-30.3, -0.7]Wilcoxon rank-sum test
Other Pre-specified
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Low-density Lipoprotein Cholesterol Levels
Median percent change from baseline to Week 12 in serum low density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day
Time frame: baseline and 12 weeks
Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMR101 (Ethyl Icosapentate) - 2 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Low-density Lipoprotein Cholesterol Levels | -2.5 Percent change from baseline |
| AMR101 (Ethyl Icosapentate) - 4 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Low-density Lipoprotein Cholesterol Levels | -4.5 Percent change from baseline |
| Placebo | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Low-density Lipoprotein Cholesterol Levels | -3.0 Percent change from baseline |
p-value: 0.676895% CI: [-12.9, 8.1]Wilcoxon rank-sum test
p-value: 0.302295% CI: [-5.4, 15.6]Wilcoxon rank-sum test
Other Pre-specified
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Non-High-Density Lipoprotein Cholesterol Levels
Median percent change from baseline to Week 12 in serum non-high density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day
Time frame: baseline and 12 weeks
Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMR101 (Ethyl Icosapentate) - 2 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Non-High-Density Lipoprotein Cholesterol Levels | 0.0 Percent change from baseline |
| AMR101 (Ethyl Icosapentate) - 4 g/Day | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Non-High-Density Lipoprotein Cholesterol Levels | -7.7 Percent change from baseline |
| Placebo | Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Non-High-Density Lipoprotein Cholesterol Levels | 7.8 Percent change from baseline |
p-value: <0.000195% CI: [-25, -11.3]Wilcoxon rank-sum test
p-value: 0.018295% CI: [-15.1, -1.4]Wilcoxon rank-sum test