ECLIPSE: Epanova® Compared to Lovaza® In a Pharmacokinetic, Single-dose, Evaluation

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01208961
• Collaborator: Radiant Research (Other)
• Enrollment: 54
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 26.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Hypertriglyceridemia	Drug: Epanova (4 g) and Lovaza (4 g); Drug: Lovaza (4 g) and Epanova (4 g)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Four-Way Crossover Study to Compare the Relative Bioavailability of a Single Dose of Epanova® With Lovaza® After a Low-Fat and High-Fat Meal
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Epanova-Lovaza-Epanova-Lovaza	Drug: Epanova (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; Other Names: Note that omefas corresponds to omega-3 carboxylic acids
Active Comparator: Lovaza-Epanova-Lovaza-Epanova	Drug: Lovaza (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; Other Names: Note that omefas corresponds to omega-3 carboxylic acids

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radiant Research	Chicago	Illinois	United States	60654

Sponsors and Collaborators

• AstraZeneca
• Radiant Research

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01208961
• Other Study ID Numbers: OM-EPA-001
• First Posted: Sep 24, 2010
• Last Update Posted: Jul 15, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by AstraZeneca: Eicosapentaenoic Acid; Docosahexaenoic Acid; Hypertriglyceridemia; Omega-3 acid ethyl esters; Omega-3 carboxylic acids; Epanova; Lovaza; bioavailability; pharmacokinetics; low-fat meal; high-fat meal
• Additional relevant MeSH terms: Hypertriglyceridemia

Study Results

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 Detail	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.

Arm/Group Title	Epanova-Lovaza-Epanova-Lovaza	Lovaza-Epanova-Lovaza-Epanova
Arm/Group Description	Epanova (4 g) and Lovaza (4 g) : Single dose of Epanova (omefas; corresponds to omega-3 carboxylic acids), 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	Lovaza (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; corresponds to omega-3 carboxylic acids), 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 of Epanova (omefas),4x1g capsules, taken with high-fat meals
Period Title: Low-Fat Period I
STARTED	27	27
COMPLETED	27	27
NOT COMPLETED	0	0
Period Title: Low-Fat Period I
STARTED	26	27
COMPLETED	26	27
NOT COMPLETED	0	0
Period Title: Low-Fat Period I
STARTED	26	26
COMPLETED	25	26
NOT COMPLETED	1	0
Period Title: Low-Fat Period I
STARTED	25	26
COMPLETED	25	26
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Subjects
Arm/Group Description	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.
Overall Participants	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.6 (11.96)
Sex: Female, Male (Count of Participants)
Female	13 24.1%
Male	41 75.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 16.7%
Not Hispanic or Latino	45 83.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	54 100%

Outcome Measures

1. Primary Outcome

Title	AUC(0-t): Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (the Final Time With a Concentration ≥ LOQ)
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epanova (Low-Fat Period)	Lovaza (Low-Fat Period)
Arm/Group Description	Single dose of Epanova (omefas), 4*1g capsules, taken after fasting 12 hours with no breakfast, followed with no-fat lunch and low-fat dinner	Single dose of Lovaza (omega-3-acid ethyl esters), 4*1g capsules, taken after fasting 12 hours with no breakfast, followed with no-fat lunch and low-fat dinner
Measure Participants	51	51
Geometric Mean (Full Range) [nmol.h/mL]	2650.1612	661.9490

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epanova (Low-Fat Period), Lovaza (Low-Fat Period)
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA on log-trans baseline-adj PK values using sequence, period, and treatments as fixed effects and subject nested within sequence as random effect
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	400.36
	Confidence Interval	(2-Sided) 90%; 326.87 to 490.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUC(Inf): Area Under the Plasma Concentration-time Curve From 0 to Infinity
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epanova (Low-Fat Period)	Lovaza (Low-Fat Period)
Arm/Group Description	Single dose of Epanova (omefas), 4*1g capsules, taken after fasting 12 hours with no breakfast, followed with no-fat lunch and low-fat dinner	Single dose of Lovaza (omega-3-acid ethyl esters), 4*1g capsules, taken after fasting 12 hours with no breakfast, followed with no-fat lunch and low-fat dinner
Measure Participants	51	51
Geometric Mean (Full Range) [nmol.h/mL]	5219.56	803.42

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epanova (Low-Fat Period), Lovaza (Low-Fat Period)
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments	ANOVA model with baseline value as covariate, and treatment and user/non-user of lipid-altering drugs as factors. LSM estimate performed on log-scale
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Mans
	Estimated Value	649.66
	Confidence Interval	(2-Sided) 90%; 511.75 to 824.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	C(Max): Maximum Plasma Concentration
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epanova (Low-Fat Period)	Lovaza (Low-Fat Period)
Arm/Group Description	Single dose of Epanova (omefas), 4*1g capsules, taken after fasting 12 hours with no breakfast, followed with no-fat lunch and low-fat dinner	Single dose of Lovaza (omega-3-acid ethyl esters), 4*1g capsules, taken after fasting 12 hours with no breakfast, followed with no-fat lunch and low-fat dinner
Measure Participants	51	51
Geometric Mean (Full Range) [nmol/mL]	225.7920	61.0818

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epanova (Low-Fat Period), Lovaza (Low-Fat Period)
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	369.66
	Confidence Interval	(2-Sided) 90%; 301.74 to 452.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	The adverse event safety results were grouped and analyzed for the entire population since the OM-3 FFA and OM-3 EE treatments were single-dose administrations received by all subjects and the protocol was not developed as an exposure-response study design.
Arm/Group Title	All Subjects
Arm/Group Description	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.
All Cause Mortality
	All Subjects
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	0/54 (0%)
Other (Not Including Serious) Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	28/54 (51.9%)
Infections and infestations
Diarrhoea	9/54 (16.7%)	10
Metabolism and nutrition disorders
Hyperglycaemia	4/54 (7.4%)	4
Nervous system disorders
Dizziness	5/54 (9.3%)	5
Headache	10/54 (18.5%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Individual investigators may publish data arising from their own subjects. The PI will provide the Sponsor with copies of written publications (including abstracts and posters)at least 60 days in advance of submission. Data will be reviewed by all participating investigators prior to publication. The Sponsor will have 60 days to review all definitive publications, such as manuscripts and book chapters, and a minimum of 30 days to review all abstracts.