An Open-Label Crossover Study to Compare the Relative Bioavailability, Efficacy and Safety of Epanova® and Lovaza® in Men and Women with a History of Pancreatitis - ECLIPSEIV

Study identifier:D5880C00003

ClinicalTrials.gov identifier:NCT02189252

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Randomized, Open-Label Crossover Study to Compare the Relative Bioavailability, Efficacy, and Safety of Epanova® and Lovaza® in Men and Women with a History of Pancreatitis

Medical condition

severe hypertriglyceridemia

Phase

Phase 1

Healthy volunteers

Study drug

Epanova, Lovaza

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 01 Oct 2014

Primary Completion Date: 01 Jul 2015

Study Completion Date: 01 Jul 2015

Study design

Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 May 2016 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Male or female, ≥18 years of age;
2. History of serum TG concentration ≥500 mg/dL within the past 5 years;
3. Have at least one episode of documented hospitalization for pancreatitis due to hypertriglyceridemia in his/her lifetime;
4. Have no health conditions that would prevent him/her from fulfilling the study
requirements as judged by the Investigator on the basis of physical examination, ECG, medical history, and routine laboratory test results;
5. Willing to maintain his/her current activity level and to follow either the NCEP TLC diet with a caloric target for weight maintenance or a prescribed low-fat diet during the screening, treatment, and washout periods (Visits 1 through 6b; Weeks -4 through 12);
6. Willing to eat the standardized breakfast, lunch, and dinner meals and snacks before and during Visits 4b and 6b (Weeks 4 and 12);
7. Willing to abstain from alcohol consumption and avoid vigorous physical activity for 48 hours prior to Visits 3 through 6b (Weeks 0 through 12); and
8. Subject understands the study procedures and is willing and able to sign the informed consent form to participate in the study and the Health Insurance Portability and Accountability Act authorization for release of relevant protected health information to the Investigators and study personnel.

Exclusion Criteria

1.An allergy or intolerance to omega-3 fatty acids, omega-3-acid ethyl esters, fish, or any of the components of the standardized breakfast, lunch, or dinner meals or snacks (as described to them by study staff)
2. Poorly controlled hypertension (resting blood pressure ≥160 mmHg systolic and/or ≥100 mmHg diastolic) prior to randomization (Visit 3 [Week 0])
3. A history of cancer (other than basal cell carcinoma) in the last 2 years
4. A recent 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), aortic aneurysm or resection, carotid endarterectomy, or revascularization procedure within the 6 months prior to Visit 1

Location

Research Site

Philadelphia, PA, United States

Location

Research Site

Kansas City, KS, United States

Location

Research Site

Chocoutimi, Quebec, Canada

Location

Research Site

Cincinnati, OH, United States

Arms	Assigned Interventions
Active Comparator: E4:L4 Crossover Sequence	-
Active Comparator: L4:E4 Crossover Sequence	-
Active Comparator: E2:L4 Crossover Sequence	-
Active Comparator: L4:E2 Crossover Sequence	-

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study subjects were recruited at 6 sites. In total, 30 subjects were screened, of which 15 were randomized to 1 of 4 treatment sequences.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No applicable

Reporting Groups

	Description
Treatment Sequence 1	Epanova 4g per day: Lovaza 4g per day
Treatment Sequence 2	Lovaza 4 g per day:Epanova 4 g per day : 4 subjects
Treatment Sequence 3	Epanova 2g per day:Lovaza 4g per day:
Treatment Sequence 4	Lovaza 4g per day:Epanova 2g per day:

Participant Flow for 2 periods

Period 1: Period 1 (Visit 4b, Week 4)

	Treatment Sequence 1	Treatment Sequence 2	Treatment Sequence 3	Treatment Sequence 4
STARTED	4	4	3	4
COMPLETED	4	2	3	4
NOT COMPLETED	0	2	0	0
Withdrawal by Subject	0	1	0	0
Adverse Event	0	1	0	0

Period 2: Period 2 (Visit6b, Week 12)

	Treatment Sequence 1	Treatment Sequence 2	Treatment Sequence 3	Treatment Sequence 4
STARTED	4	2	3	4
COMPLETED	4	2	3	4
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Treatment Sequence 1	Epanova 4 g per day:Lovaza 4 g per day
Treatment Sequence 2	Lovaza 4 g per day:Epanova 4 g per day : 4 subjects
Treatment Sequence 3	Epanova 2 g per day:Lovaza 4 g per day
Treatment Sequence 4	Lovaza 4 g per day:Epanova 2 g per day: 4 subjects

Baseline Measures

	Treatment Sequence 1	Treatment Sequence 2	Treatment Sequence 3	Treatment Sequence 4	Total
Number of Participants [units: Participants]	4	4	3	4	15
Age Continuous [units: years] Mean ± Standard Deviation	47.5 ± 6.86	46.0 ± 13.09	53.0 ± 16.46	53.5 ± 11.27	49.8 ± 11.16
Gender, Male/Female [units: Participants]
Female	1	3	1	0	5
Male	3	1	2	4	10

Outcome Measures

1. Primary Outcome Measure: Baseline-adjusted AUC0-24 for plasma Total EPA + Total DHA [ Time Frame: participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between. ]

Measure Type	Primary
Measure Name	Baseline-adjusted AUC0-24 for plasma Total EPA + Total DHA
Measure Description	AUC0-24: Area under the plasma concentration versus time curve, from time 0 to 24 hours after start of the meal
Time Frame	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population

Reporting Groups

	Description
Epanova 2 g	Once daily (QD)
Epanova 4 g	Once daily (QD)
Lovaza 4 g	Once daily (QD)

Measured Values

	Epanova 2 g	Epanova 4 g	Lovaza 4 g
Number of Participants Analyzed [units:participants]	6	6	12
Baseline-adjusted AUC0-24 for plasma Total EPA + Total DHA [units: hr*nmol/mL] Geometric Mean (Geometric Coefficient of Variation)	17000 (121.7 %)	18000 (104.6 %)	12500 (80.0 %)

Statistical Analysis 1 for Baseline-adjusted AUC0-24 for plasma Total EPA + Total DHA

Groups^[1]	Epanova 4 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.2702
Other^[5]	160.05
95% Confidence Interval	( 64.71 to 395.82 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	In order to address the issue of multiple testing while maintaining overall type I error, a closed testing sequence was used involving 4 analyses stated in the primary objective of this study. In total, 4 statistical tests, each at a significance level of 5%, were carried along the fixed sequence until the first statistically non-significant treatment difference was observed (i.e. p-value>0.05). This is the first test in the fixed testing sequence.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The closed sequential testing procedure stopped at this step as the P Value is greater than 0.05.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Baseline-adjusted AUC0-24 for plasma Total EPA + Total DHA

Groups^[1]	Epanova 2 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.6367
Other^[5]	121.61
95% Confidence Interval	( 49.17 to 300.76 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	In order to address the issue of multiple testing while maintaining overall type I error, a closed testing sequence was used involving 4 analyses stated in the primary objective of this study. In total, 4 statistical tests, each at a significance level of 5%, were carried along the fixed sequence until the first statistically non-significant treatment difference was observed (i.e. p-value>0.05). This is the second test in the fixed testing sequence.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The p-value was only interpreted descriptively
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Baseline-adjusted Cmax for plasma Total EPA + Total DHA [ Time Frame: participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between. ]

Measure Type	Primary
Measure Name	Baseline-adjusted Cmax for plasma Total EPA + Total DHA
Measure Description	Cmax: Maximum measured plasma concentration over the time span specified
Time Frame	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK population

Reporting Groups

	Description
Epanova 2 g	Once daily (QD)
Epanova 4 g	Once daily (QD)
Lovaza 4 g	Once daily (QD)

Measured Values

	Epanova 2 g	Epanova 4 g	Lovaza 4 g
Number of Participants Analyzed [units:participants]	6	6	12
Baseline-adjusted Cmax for plasma Total EPA + Total DHA [units: nmol/mL] Geometric Mean (Geometric Coefficient of Variation)	1090 (78.6%)	1200 (70.2%)	712 (76.7%)

Statistical Analysis 1 for Baseline-adjusted Cmax for plasma Total EPA + Total DHA

Groups^[1]	Epanova 4 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.0511
Other^[5]	193.91
95% Confidence Interval	( 99.61 to 377.47 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	In order to address the issue of multiple testing while maintaining overall type I error, a closed testing sequence was used involving 4 analyses stated in the primary objective of this study. In total, 4 statistical tests, each at a significance level of 5%, were carried along the fixed sequence until the first statistically non-significant treatment difference was observed (i.e. p-value>0.05). This is the third test in the fixed testing sequence.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The p-value was only interpreted descriptively
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Baseline-adjusted Cmax for plasma Total EPA + Total DHA

Groups^[1]	Epanova 2 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.3543
Other^[5]	133.32
95% Confidence Interval	( 68.49 to 259.52 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	In order to address the issue of multiple testing while maintaining overall type I error, a closed testing sequence was used involving 4 analyses stated in the primary objective of this study. In total, 4 statistical tests, each at a significance level of 5%, were carried along the fixed sequence until the first statistically non-significant treatment difference was observed (i.e. p-value>0.05). This is the fourth test in the fixed testing sequence.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The p-value was only interpreted descriptively
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Baseline-adjusted AUC0-24 for plasma Total EPA [ Time Frame: participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between. ]

Measure Type	Secondary
Measure Name	Baseline-adjusted AUC0-24 for plasma Total EPA
Measure Description
Time Frame	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Population

Reporting Groups

	Description
Epanova 2 g	Once daily (QD)
Epanova 4 g	Once daily (QD)
Lovaza 4 g	Once daily (QD)

Measured Values

	Epanova 2 g	Epanova 4 g	Lovaza 4 g
Number of Participants Analyzed [units:participants]	6	6	12
Baseline-adjusted AUC0-24 for plasma Total EPA [units: hr*ug/mL] Geometric Mean (Geometric Coefficient of Variation)	3510 (117.8%)	3930 (83.0%)	1730 (78.4%)

Statistical Analysis 1 for Baseline-adjusted AUC0-24 for plasma Total EPA

Groups^[1]	Epanova 4 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.0210
Other^[5]	259.19
95% Confidence Interval	( 119.75 to 560.99 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Baseline-adjusted AUC0-24 for plasma Total EPA

Groups^[1]	Epanova 2 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.1256
Other^[5]	177.95
95% Confidence Interval	( 82.22 to 385.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Baseline-adjusted Cmax for plasma Total EPA [ Time Frame: participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between. ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Cmax for plasma Total EPA
Measure Description
Time Frame	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Population

Reporting Groups

	Description
Epanova 2 g	Once daily (QD)
Epanova 4 g	Once daily (QD)
Lovaza 4 g	Once daily (QD)

Measured Values

	Epanova 2 g	Epanova 4 g	Lovaza 4 g
Number of Participants Analyzed [units:participants]	6	6	12
Baseline-adjusted Cmax for plasma Total EPA [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	221 (83.0%)	255 (65.7%)	100 (74.9%)

Statistical Analysis 1 for Baseline-adjusted Cmax for plasma Total EPA

Groups^[1]	Epanova 4 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.0025
Other^[5]	298.91
95% Confidence Interval	( 164.32 to 543.74 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The p-value was only interpreted descriptively
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Baseline-adjusted Cmax for plasma Total EPA

Groups^[1]	Epanova 2 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.0418
Other^[5]	187.28
95% Confidence Interval	( 102.95 to 340.66 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The p-value was only interpreted descriptively
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Baseline-adjusted AUC0-24 for plasma Total DHA [ Time Frame: participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between. ]

Measure Type	Secondary
Measure Name	Baseline-adjusted AUC0-24 for plasma Total DHA
Measure Description
Time Frame	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Population

Reporting Groups

	Description
Epanova 2 g	Once daily (QD)
Epanova 4 g	Once daily (QD)
Lovaza 4 g	Once daily (QD)

Measured Values

	Epanova 2 g	Epanova 4 g	Lovaza 4 g
Number of Participants Analyzed [units:participants]	6	6	12
Baseline-adjusted AUC0-24 for plasma Total DHA [units: hr*ug/mL] Geometric Mean (Geometric Coefficient of Variation)	1710 (136.3%)	1550 (195.2%)	2190 (86.9%)

Statistical Analysis 1 for Baseline-adjusted AUC0-24 for plasma Total DHA

Groups^[1]	Epanova 4 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.6833
Other^[5]	79.36
95% Confidence Interval	( 22.95 to 274.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Baseline-adjusted AUC0-24 for plasma Total DHA

Groups^[1]	Epanova 2 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.5220
Other^[5]	69.39
95% Confidence Interval	( 20.07 to 239.98 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Baseline-adjusted Cmax for plasma Total DHA [ Time Frame: This is a crossover study with two treatment periods. The estimated treatment effects were based on the within-subject comparison between the two treatments, each having a 4-week duration and a 4-week wash off period in between. ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Cmax for plasma Total DHA
Measure Description
Time Frame	This is a crossover study with two treatment periods. The estimated treatment effects were based on the within-subject comparison between the two treatments, each having a 4-week duration and a 4-week wash off period in between.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Population

Reporting Groups

	Description
Epanova 2 g	Once daily (QD)
Epanova 4 g	Once daily (QD)
Lovaza 4 g	Once daily (QD)

Measured Values

	Epanova 2 g	Epanova 4 g	Lovaza 4 g
Number of Participants Analyzed [units:participants]	6	6	12
Baseline-adjusted Cmax for plasma Total DHA [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	116 (76.1%)	118 (89.2%)	128 (82.3%)

Statistical Analysis 1 for Baseline-adjusted Cmax for plasma Total DHA

Groups^[1]	Epanova 4 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.9034
Other^[5]	104.78
95% Confidence Interval	( 44.92 to 244.41 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Baseline-adjusted Cmax for plasma Total DHA

Groups^[1]	Epanova 2 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.5782
Other^[5]	80.58
95% Confidence Interval	( 34.55 to 187.95 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Baseline-adjusted AUC0-24 for plasma Total DPA [ Time Frame: participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between. ]

Measure Type	Secondary
Measure Name	Baseline-adjusted AUC0-24 for plasma Total DPA
Measure Description
Time Frame	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Population

Reporting Groups

	Description
Epanova 2 g	Once daily (QD)
Epanova 4 g	Once daily (QD)
Lovaza 4 g	Once daily (QD)

Measured Values

	Epanova 2 g	Epanova 4 g	Lovaza 4 g
Number of Participants Analyzed [units:participants]	6	6	12
Baseline-adjusted AUC0-24 for plasma Total DPA [units: hr*ug/mL] Geometric Mean (Geometric Coefficient of Variation)	244 (225.3%)	380 (240.9%)	108 (374.3%)

Statistical Analysis 1 for Baseline-adjusted AUC0-24 for plasma Total DPA

Groups^[1]	Epanova 4 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.0391
Other^[5]	753.75
95% Confidence Interval	( 112.03 to 5071.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Baseline-adjusted AUC0-24 for plasma Total DPA

Groups^[1]	Epanova 2 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.9578
Other^[5]	104.98
95% Confidence Interval	( 15.60 to 706.33 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Baseline-adjusted Cmax for plasma Total DPA [ Time Frame: participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between. ]

Measure Type	Secondary
Measure Name	Baseline-adjusted Cmax for plasma Total DPA
Measure Description
Time Frame	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Population

Reporting Groups

	Description
Epanova 2 g	Once daily (QD)
Epanova 4 g	Once daily (QD)
Lovaza 4 g	Once daily (QD)

Measured Values

	Epanova 2 g	Epanova 4 g	Lovaza 4 g
Number of Participants Analyzed [units:participants]	6	6	12
Baseline-adjusted Cmax for plasma Total DPA [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	23.0 (64.2%)	26.4 (83.3%)	11.1 (128.9%)

Statistical Analysis 1 for Baseline-adjusted Cmax for plasma Total DPA

Groups^[1]	Epanova 4 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.0186
Other^[5]	376.64
95% Confidence Interval	( 128.55 to 1103.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
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Statistical Analysis 2 for Baseline-adjusted Cmax for plasma Total DPA

Groups^[1]	Epanova 2 g, Lovaza 4 g
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.5955
Other^[5]	131.74
95% Confidence Interval	( 44.97 to 386.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Epanova 2 g (I)	Treatment period I
Epanova 4 g (I)	Treatment period I
Lovaza 4 g (I)	Treatment period I
Epanova 2 g (II)	Treatment period II
Epanova 4 g (II)	Treatment period II
Lovaza 4 g (II)	Treatment period II

Serious Adverse Events

	Epanova 2 g (I)	Epanova 4 g (I)	Lovaza 4 g (I)	Epanova 2 g (II)	Epanova 4 g (II)	Lovaza 4 g (II)
Total, serious adverse events
# participants affected / at risk	0/3 (0.00%)	0/4 (0.00%)	0/8 (0.00%)	0/4 (0.00%)	0/2 (0.00%)	0/7 (0.00%)

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Epanova 2 g (I)	Treatment period I
Epanova 4 g (I)	Treatment period I
Lovaza 4 g (I)	Treatment period I
Epanova 2 g (II)	Treatment period II
Epanova 4 g (II)	Treatment period II
Lovaza 4 g (II)	Treatment period II

Other Adverse Events

Epanova 2 g (I)

Epanova 4 g (I)

Lovaza 4 g (I)

Epanova 2 g (II)

Epanova 4 g (II)

Lovaza 4 g (II)

Total, other (not including serious) adverse events

# participants affected / at risk

2/3 (66.67%)

3/4 (75.00%)

5/8 (62.50%)

3/4 (75.00%)

2/2 (100.00%)

1/7 (14.29%)

Blood and lymphatic system disorders

Any¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Blood and lymphatic system disorders

Anemia ¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Gastrointestinal disorders

Any¹,^†

# participants affected / at risk

2/3 (66.67%)

2/4 (50.00%)

2/8 (25.00%)

2/4 (50.00%)

1/2 (50.00%)

0/7 (0.00%)

Gastrointestinal disorders

Diarrhea¹,^†

# participants affected / at risk

1/3 (33.33%)

1/4 (25.00%)

0/8 (0.00%)

1/4 (25.00%)

1/2 (50.00%)

0/7 (0.00%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/3 (33.33%)

1/4 (25.00%)

1/8 (12.50%)

1/4 (25.00%)

0/2 (0.00%)

0/7 (0.00%)

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/8 (0.00%)

0/4 (0.00%)

1/2 (50.00%)

0/7 (0.00%)

Gastrointestinal disorders

Dyspepsia ¹,^†

# participants affected / at risk

1/3 (33.33%)

0/4 (0.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

General disorders

Any¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

3/8 (37.50%)

2/4 (50.00%)

0/2 (0.00%)

0/7 (0.00%)

General disorders

Local swelling¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

2/8 (25.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

General disorders

Asthenia¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Infections and infestations

Any¹,^†

# participants affected / at risk

1/3 (33.33%)

2/4 (50.00%)

0/8 (0.00%)

1/4 (25.00%)

1/2 (50.00%)

0/7 (0.00%)

Infections and infestations

Abdominal abscess¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Infections and infestations

Influenza¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/8 (0.00%)

1/4 (25.00%)

0/2 (0.00%)

0/7 (0.00%)

Infections and infestations

Nasopharyngitis ¹,^†

# participants affected / at risk

1/3 (33.33%)

0/4 (0.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Infections and infestations

Pharyngitis streptococcal¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Infections and infestations

Viral upper respiratory tract infection¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/8 (0.00%)

0/4 (0.00%)

1/2 (50.00%)

0/7 (0.00%)

Musculoskeletal and connective tissue disorders

Any¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

2/8 (25.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Musculoskeletal and connective tissue disorders

Myopathy¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Musculoskeletal and connective tissue disorders

Pain in extremity ¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Nervous system disorders

Any¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

1/7 (14.29%)

Nervous system disorders

Headache ¹,^†

# participants affected / at risk

0/3 (0.00%)

1/4 (25.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Nervous system disorders

Lethargy ¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

1/7 (14.29%)

Nervous system disorders

Somnolence ¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Renal and urinary disorders

Any¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Renal and urinary disorders

Renal failure¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

1/8 (12.50%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Respiratory, thoracic and mediastinal disorders

Any¹,^†

# participants affected / at risk

1/3 (33.33%)

0/4 (0.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

1/3 (33.33%)

0/4 (0.00%)

0/8 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

0/7 (0.00%)

Skin and subcutaneous tissue disorders

Any¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/8 (0.00%)

1/4 (25.00%)

0/2 (0.00%)

0/7 (0.00%)

Skin and subcutaneous tissue disorders

Xanthelasma¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/8 (0.00%)

1/4 (25.00%)

0/2 (0.00%)

0/7 (0.00%)

Skin and subcutaneous tissue disorders

Xanthoma¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

0/8 (0.00%)

1/4 (25.00%)

0/2 (0.00%)

0/7 (0.00%)

General disorders

Fatigue¹,^†

# participants affected / at risk

0/3 (0.00%)

0/4 (0.00%)

2/8 (25.00%)

2/4 (50.00%)

0/2 (0.00%)

0/7 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 16.1

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Hong Yang, Study Statistician
Organization:	AstraZeneca AB
Phone	+46-(0)317762397
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

Tjerk de Bruin

+1 301 398 0515

Investigators

Principal Investigator

Andrea L Lawless

Biofortis, Inc Addison IL 60101

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Trial Results Summaries