Severe Hypertriglyceridemia
Conditions
Keywords
Eicosapentaenoic Acid, Docosahexaenoic Acid, Hypertriglyceridemia, Omega-3 acid ethyl esters, Omega-3 carboxylic acids, Epanova, Lovaza, bioavailability, pharmacokinetics, low-fat meal, high-fat meal
Brief summary
The objectives of this study are to compare the relative bioavailabilities of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma from a single dose of Epanova or Lovaza during periods of high- and low -fat consumption.
Interventions
DRUGEpanova (4 g) and Lovaza (4 g)
Single dose of Epanova (omefas), 4x1g capsules, taken with low-fat meals, 7 day washout followed by single dose of Lovaza (omega-3-acid ethyl esters), 4x1g capsules, taken with low-fat meals, 7 day washout followed by single dose of Epanova (omefas), 4x1g capsules, taken with high-fat meals, 7 day washout followed by single dose of Lovaza (omega-3-acid ethyl esters, 4x1g capsules, taken with high-fat meals
DRUGLovaza (4 g) and Epanova (4 g)
Single dose of Lovaza (omega-3-acid ethyl esters), 4x1g capsules, taken with low-fat meals, 7 day washout followed by single dose of Epanova (omefas), 4x1g capsules, taken with low-fat meals, 7 day washout followed by single dose of Lovaza (omega-3-acid ethyl esters,4x1g capsules, taken with high-fat meals, 7 day washout followed by single dose ofEpanova (omefas),4x1g capsules, taken with high-fat meals
Sponsors
Radiant Research
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Men or women, aged ≥18. * Normal healthy volunteers based on medical history, clinical assessments, and laboratory assessments. * Body mass index 25-35 kg/m2. * Willingness to maintain current activity level. * Willingness to adhere to the Therapeutic Lifestyle Changes (TLC)diet during screening and treatment washout periods.
Exclusion criteria
* Intolerance to omega-3 fatty acids, ethyl esters, or fish. * Unable or unwilling to eat the study meals. * Use of fish oil, other EPA or DHA containing supplements, or EPA and/or DHA fortified foods within 60 days of Visit 2, or during the study. * Consumption of any fish within 7 days of Visit 2, or during the study. * Use of flaxseed, perilla seed, hemp, spirulina, or black currant oils within 7 days of Visit 2, or during the study. * History of malabsorption syndrome, Crohn's disease, acute or chronic pancreatitis, pancreatic insufficiency, small bowel resection. * Women who are pregnant, lactating, or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since last menstrual period. Examples of acceptable contraceptive methods include abstinence, intrauterine device (IUD) or double barrier method, oral or injectable contraceptives. * Recent history (past 12 months) of drug abuse or alcohol abuse. Alcohol abuse will be defined as \>14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1.5 oz hard liquor). * Exposure to any investigational product, within 28 days prior to Visit 1. * 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 |
|---|---|---|
| AUC(0-t): Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (the Final Time With a Concentration ≥ LOQ) | Blood samples were obtained pre-dose at -1.0, -0.5, and 0 hours and after dose administration at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours. | Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation. |
| AUC(Inf): Area Under the Plasma Concentration-time Curve From 0 to Infinity | Blood samples were obtained pre-dose at -1.0, -0.5, and 0 hours and after dose administration at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours. | Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation. |
| C(Max): Maximum Plasma Concentration | Blood samples were obtained pre-dose at -1.0, -0.5, and 0 hours and after dose administration at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours. | Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation. |
Countries
United States
Participant flow
Recruitment details
The enrollment period started October 2010 and the last subject visit was November 2010. All subjects were qualified at the clinical site and eligibility was determined by the PI (one US clinical site).
Pre-assignment details
This was a 4-way crossover study with a minimum 7-day washout period between each treatment. Subjects were healthy volunteers aged ≥ 18 with a body mass index 25-35 kg/m2 and who were not intolerant to omega-3 products or fish. Subjects were instructed to follow the TLC diet and abstain from omega-3 products or fish for screening and all periods.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects All subjects received both Epanova (E) and Lovaza (L), and both under fasted and fed conditions. Subjects were randomized 1:1 to one of the following treatment period sequences: ELEL or LELE. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| High-Fat Period III | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 44.6 years STANDARD_DEVIATION 11.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 54 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 28 / 54 |
| serious Total, serious adverse events | 0 / 54 |
Outcome results
Primary
AUC(0-t): Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (the Final Time With a Concentration ≥ LOQ)
Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation.
Time frame: Blood samples were obtained pre-dose at -1.0, -0.5, and 0 hours and after dose administration at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Epanova (Low-Fat Period) | AUC(0-t): Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (the Final Time With a Concentration ≥ LOQ) | 2650.1612 nmol.h/mL |
| Lovaza (Low-Fat Period) | AUC(0-t): Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (the Final Time With a Concentration ≥ LOQ) | 661.9490 nmol.h/mL |
Comparison: Results for the analyses of the High-Fat Periods were not posted because the critical comparison was the response of Lovaza versus Epanova to the clinically relevant low-fat diet to be used as adjunct in hypertriglyceridemia.p-value: <0.00190% CI: [326.87, 490.36]ANOVA
Primary
AUC(Inf): Area Under the Plasma Concentration-time Curve From 0 to Infinity
Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation.
Time frame: Blood samples were obtained pre-dose at -1.0, -0.5, and 0 hours and after dose administration at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Epanova (Low-Fat Period) | AUC(Inf): Area Under the Plasma Concentration-time Curve From 0 to Infinity | 5219.56 nmol.h/mL |
| Lovaza (Low-Fat Period) | AUC(Inf): Area Under the Plasma Concentration-time Curve From 0 to Infinity | 803.42 nmol.h/mL |
Comparison: Results for the analyses of the High-Fat Periods were not posted because the critical comparison was the response of Lovaza versus Epanova to the clinically relevant low-fat diet to be used as adjunct in hypertriglyceridemia.p-value: <0.0190% CI: [511.75, 824.75]ANOVA
Primary
C(Max): Maximum Plasma Concentration
Analyses of the outcome measures presented are for baseline-adjusted data for total (esterified and unesterfied) EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation.
Time frame: Blood samples were obtained pre-dose at -1.0, -0.5, and 0 hours and after dose administration at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Epanova (Low-Fat Period) | C(Max): Maximum Plasma Concentration | 225.7920 nmol/mL |
| Lovaza (Low-Fat Period) | C(Max): Maximum Plasma Concentration | 61.0818 nmol/mL |
Comparison: Results for the analyses of the High-Fat Periods were not posted because the critical comparison was the response of Lovaza versus Epanova to the clinically relevant low-fat diet to be used as adjunct in hypertriglyceridemia.p-value: <0.00190% CI: [301.74, 452.86]ANOVA