A Study to Investigate How Common Pancreatic Exocrine Ins... | NCT02370537

ID	Type	Description	Link
2014-003511-11	EudraCT Number

Label	Type	Description	Intervention Names
Sequence AB	Experimental	A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) at Visit 4, followed by 10 to 14 days washout, followed by a single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) at Visit 7.	Drug: Epanova® (omega-3 carboxylic acids) Drug: Omacor® (omega-3-acid ethyl esters)
Sequence BA	Experimental	A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) at Visit 4, followed by 10 to 14 days washout, followed by a single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) at Visit 7.	Drug: Epanova® (omega-3 carboxylic acids) Drug: Omacor® (omega-3-acid ethyl esters)

Name	Type	Description	Arm Group Labels	Other Names
Epanova® (omega-3 carboxylic acids)	Drug	4 g (administered orally as 4 x 1 g capsules)	Sequence AB Sequence BA

Measure	Description	Time Frame
Part A: Serum TG Level.	For Part A, the distribution of serum TG levels by the degree of pancreatic exocrine insufficiency (PEI) was assessed in patients with Type 2 Diabetes Mellitus (T2DM).	7 days after enrollment.
Part B: Baseline Corrected Area Under the Plasma Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) for Total Eicosapentaenoic Acid (EPA) Following Administration of EPANOVA® and OMACOR®.	Baseline corrected AUC(0-last) was measured for total EPA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.	Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.
Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®.	Baseline corrected AUC(0-last) was measured for total DHA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.	Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.
Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®.	Baseline corrected AUC(0-last) was measured for the sum of EPA and DHA (total EPA+DHA) following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.	Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Aarhus			Denmark
Research Site

PubMed Identifier	Type	Citation	Retractions
29802077	Derived	Lindkvist B, Nilsson C, Kvarnstrom M, Oscarsson J. Importance of pancreatic exocrine dysfunction in patients with type 2 diabetes: A randomized crossover study. Pancreatology. 2018 Jul;18(5):550-558. doi: 10.1016/j.pan.2018.05.483. Epub 2018 May 19.

ID	Title	Description
FG000	Low FEC (EPANOVA® and OMACOR®)	Part A investigated serum lipids, especially triglycerides (TGs) and faecal elastase-1 concentration (FEC) as a measure of pancreatic exocrine function in the study population. Patients in the Low FEC group were determined to have FEC levels <100 microgram per gram (mcg/g). No treatment was administered in Part A which was a recruitment phase for Part B. In Part B, study treatment was administered at Visit 4 and Visit 7 with a randomised crossover design to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part A: Serum TG Level.

For Part A, the distribution of serum TG levels by the degree of pancreatic exocrine insufficiency (PEI) was assessed in patients with Type 2 Diabetes Mellitus (T2DM).

The Per Protocol Analysis Set included all enrolled patients without an important protocol deviation.

Posted

Mean

Standard Deviation

millimole per litre (mmol/L)

7 days after enrollment.

ID	Title	Description
OG000	Low FEC (EPANOVA® and OMACOR®)	Part A investigated serum lipids, especially TGs and FEC to assess the relationship between serum TGs and degree of pancreatic exocrine function (as measured by FEC) in the study population. Patients in the Low FEC group were determined to have FEC levels <100 mcg/g. No treatment was administered in Part A which was a recruitment phase for Part B.
OG001	Intermediate FEC (EPANOVA® and OMACOR®)	Part A investigated serum lipids, especially TGs and FEC to assess the relationship between serum TGs and degree of pancreatic exocrine function (as measured by FEC) in the study population. Patients in the Intermediate FEC group were determined to have FEC levels ≥100 mcg/g to <200 mcg/g. No treatment was administered in Part A which was a recruitment phase for Part B.
OG002	Normal FEC (EPANOVA® and OMACOR®)	Part A investigated serum lipids, especially TGs and FEC to assess the relationship between serum TGs and degree of pancreatic exocrine function (as measured by FEC) in the study population. Patients in the Normal FEC group were determined to have FEC levels ≥200 mcg/g. No treatment was administered in Part A which was a recruitment phase for Part B.

Units	Counts
Participants	OG00015 OG00116 OG002278

Title

Denominators

Categories

Title	Measurements
	OG0002.07± 0.63 OG0011.68± 0.57 OG0022.00± 1.16

Primary

Part B: Baseline Corrected Area Under the Plasma Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) for Total Eicosapentaenoic Acid (EPA) Following Administration of EPANOVA® and OMACOR®.

Baseline corrected AUC(0-last) was measured for total EPA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.

The Pharmacokinetic (PK) Analysis Set included all randomised patients who received at least one dose of study treatment in Part B and had at least one post-dose PK measurement without any important protocol deviations. 3 subjects were excluded from the analysis for AUC(0-last) due to missing sample results at 48 hours.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours*mcg per millilitre (h*mcg/mL)

Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.

ID	Title	Description
OG000	Low FEC (EPANOVA®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).
OG001	Low FEC (OMACOR®)

Primary

Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®.

Baseline corrected AUC(0-last) was measured for total DHA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.

The PK Analysis Set included all randomised patients who received at least one dose of study treatment in Part B and had at least one post-dose PK measurement without any protocol deviations. 3 subjects were excluded from the analysis for AUC(0-last) due to missing sample results at 48 hours.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*mcg/mL

Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.

ID	Title	Description
OG000	Low FEC (EPANOVA®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).
OG001	Low FEC (OMACOR®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).

Primary

Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®.

Baseline corrected AUC(0-last) was measured for the sum of EPA and DHA (total EPA+DHA) following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*nanomole/mL (h*nmol/mL)

Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.

ID	Title	Description
OG000	Low FEC (EPANOVA®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).
OG001	Low FEC (OMACOR®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).

Primary

Part B: Baseline Corrected Maximum Plasma Drug Concentration (Cmax) for Total EPA Following Administration of EPANOVA® and OMACOR®.

Baseline corrected Cmax was measured for total EPA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.

The PK Analysis Set included all randomised patients who received at least one dose of study treatment in Part B and had at least one post-dose PK measurement without any important protocol deviations.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.

ID	Title	Description
OG000	Low FEC (EPANOVA®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).
OG001	Low FEC (OMACOR®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).

Primary

Part B: Baseline Corrected Cmax for Total DHA Following Administration of EPANOVA® and OMACOR®.

Baseline corrected Cmax was measured for total DHA following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.

The PK Analysis Set included all randomised patients who received at least one dose of study treatment in Part B and had at least one post-dose PK measurement without any protocol deviations.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.

ID	Title	Description
OG000	Low FEC (EPANOVA®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).
OG001	Low FEC (OMACOR®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).

Primary

Part B: Baseline Corrected Cmax for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®.

Baseline corrected Cmax was measured for the sum of EPA and DHA (total EPA+DHA) following administration of single oral doses of EPANOVA® 4 g (A) and OMACOR® 4 g (B) (2-way crossover design) to patients with T2DM and different degrees of PEI.

The PK Analysis Set included all randomised patients who received at least one dose of study treatment in Part B and had at least one post-dose PK measurement without any protocol deviations.

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol/mL

Blood samples for analysis were taken at 1, 0.5, and 0.05 hours pre-dose, to be used as baseline, and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 24 and 48 hours post-dose.

ID	Title	Description
OG000	Low FEC (EPANOVA®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).
OG001	Low FEC (OMACOR®)	In Part B, study treatment was administered at Visit 4 (Day 21+5) and Visit 7 (10 to 14 days after Visit 4) with a randomised crossover design. Patients with low FEC, <100 mcg/g were randomised in Part B to a treatment sequence: AB (a single dose of EPANOVA® 4 g followed by a single dose of OMACOR® 4 g) or BA (a single dose of OMACOR® 4 g followed by a single dose of EPANOVA® 4 g).

Title

Description

Deaths (Affected)

Deaths (At Risk)

Serious Events (Affected)

Serious Events (At Risk)

Other Events (Affected)

Other Events (At Risk)

EG000

Low FEC (EPANOVA®)

Patients had low levels (<100 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function. AEs with an onset date on or after the date of administration of EPANOVA® 4 g at Visit 4 were reported for this group.

EG001

Low FEC (OMACOR®)

Patients had low levels (<100 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function. AEs with an onset date on or after the date of administration of OMACOR® 4 g at Visit 4 were reported for this group.

EG002

Intermediate FEC (EPANOVA®)

Patients had intermediate levels (≥100 to <200 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function. AEs with an onset date on or after the date of administration of EPANOVA® 4 g at Visit 4 were reported for this group.

EG003

Intermediate FEC (OMACOR®)

Patients had intermediate levels (≥100 to <200 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function. AEs with an onset date on or after the date of administration of OMACOR® 4 g at Visit 4 were reported for this group.

EG004

Normal FEC (EPANOVA®)

Patients had normal levels (≥200 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function. AEs with an onset date on or after the date of administration of EPANOVA® 4 g at Visit 4 were reported for this group.

EG005

Normal FEC (OMACOR®)

Patients had normal levels (≥200 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function. AEs with an onset date on or after the date of administration of OMACOR® 4 g at Visit 4 were reported for this group.

Group IDs

Group Description

Statistical Method

Statistical Comment

P-Value

P-Value Comment

Parameter Type

Parameter Value

Dispersion Type

Dispersion Value

Confidence Interval Sides

Confidence Interval %

CI Lower Limit

CI Upper Limit

CI Lower Limit Comment

CI Upper Limit Comment

Estimate Comment

Tested Non-Inferiority

Non-Inferiority Type

Non-Inferiority Comment

Other Analysis Description

OG000
OG001

Back transformed results are based on the analysis of natural log-transformed data with a Linear Mixed Model containing the terms of FEC classification, treatment, FEC x treatment, sequence, and period as fixed effects and patient nested within sequence as random effect.

Geometric least-squares (GLS) Mean Ratio

0.75

2-Sided

0.52

1.10

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of least-square means (LSmeans) for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% Confidence Intervals (CIs) by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG002
OG003

GLS Mean ratio

0.48

2-Sided

0.32

0.72

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG004
OG005

GLS Mean Ratio

0.6

2-Sided

0.44

0.82

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

Group IDs

Group Description

Statistical Method

Statistical Comment

P-Value

P-Value Comment

Parameter Type

Parameter Value

Dispersion Type

Dispersion Value

Confidence Interval Sides

Confidence Interval %

CI Lower Limit

CI Upper Limit

CI Lower Limit Comment

CI Upper Limit Comment

Estimate Comment

Tested Non-Inferiority

Non-Inferiority Type

Non-Inferiority Comment

Other Analysis Description

OG000
OG001

GLS Mean Ratio

1.28

2-Sided

0.84

1.93

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG002
OG003

GLS Mean Ratio

0.80

2-Sided

0.51

1.25

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG004
OG005

GLS Mean Ratio

1.29

2-Sided

0.92

1.82

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

Group IDs

Group Description

Statistical Method

Statistical Comment

P-Value

P-Value Comment

Parameter Type

Parameter Value

Dispersion Type

Dispersion Value

Confidence Interval Sides

Confidence Interval %

CI Lower Limit

CI Upper Limit

CI Lower Limit Comment

CI Upper Limit Comment

Estimate Comment

Tested Non-Inferiority

Non-Inferiority Type

Non-Inferiority Comment

Other Analysis Description

OG000
OG001

GLS Mean Ratio

0.90

2-Sided

0.63

1.28

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG002
OG003

GLS Mean Ratio

0.58

2-Sided

0.39

0.85

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG004
OG005

GLS Mean Ratio

0.75

2-Sided

0.55

1.00

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

Group IDs

Group Description

Statistical Method

Statistical Comment

P-Value

P-Value Comment

Parameter Type

Parameter Value

Dispersion Type

Dispersion Value

Confidence Interval Sides

Confidence Interval %

CI Lower Limit

CI Upper Limit

CI Lower Limit Comment

CI Upper Limit Comment

Estimate Comment

Tested Non-Inferiority

Non-Inferiority Type

Non-Inferiority Comment

Other Analysis Description

OG000
OG001

GLS Mean Ratio

0.52

2-Sided

0.37

0.73

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG002
OG003

GLS Mean Ratio

0.46

2-Sided

0.32

0.67

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG004
OG005

GLS Mean Ratio

0.53

2-Sided

0.40

0.70

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

Group IDs

Group Description

Statistical Method

Statistical Comment

P-Value

P-Value Comment

Parameter Type

Parameter Value

Dispersion Type

Dispersion Value

Confidence Interval Sides

Confidence Interval %

CI Lower Limit

CI Upper Limit

CI Lower Limit Comment

CI Upper Limit Comment

Estimate Comment

Tested Non-Inferiority

Non-Inferiority Type

Non-Inferiority Comment

Other Analysis Description

OG000
OG001

GLS Mean Ratio

1.02

2-Sided

0.77

1.36

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of least-squares LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG002
OG003

GLS mean Ratio

0.92

2-Sided

0.67

1.25

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG004
OG005

GLS Mean Ratio

1.11

2-Sided

0.88

1.40

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

Group IDs

Group Description

Statistical Method

Statistical Comment

P-Value

P-Value Comment

Parameter Type

Parameter Value

Dispersion Type

Dispersion Value

Confidence Interval Sides

Confidence Interval %

CI Lower Limit

CI Upper Limit

CI Lower Limit Comment

CI Upper Limit Comment

Estimate Comment

Tested Non-Inferiority

Non-Inferiority Type

Non-Inferiority Comment

Other Analysis Description

OG000
OG001

GLS Mean

0.68

2-Sided

0.49

0.92

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG002
OG003

GLS Mean Ratio

0.60

2-Sided

0.42

0.84

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

OG004
OG005

GLS Mean Ratio

0.70

2-Sided

0.54

0.90

OMACOR®/EPANOVA®

Yes

Non-Inferiority or Equivalence

The exposure of a single dose of EPANOVA® 4 g (reference) relative to OMACOR® 4 g (test) was estimated by degree of pancreatic exocrine function using level of FEC. Natural log estimates of LSmeans for each treatment and differences of the LSmeans (OMACOR®-EPANOVA®) along with 90% CIs by degree of pancreatic exocrine function using level of FEC were exponentiated.

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected15 at risk EG0020 events0 affected13 at risk EG0030 events0 affected12 at risk EG0040 events0 affected23 at risk EG0050 events0 affected23 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected15 at risk EG0020 events0 affected13 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected15 at risk EG0020 events0 affected13 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected15 at risk EG0020 events0 affected13 at risk EG003
Dry Mouth	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected15 at risk EG0020 events0 affected13 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected15 at risk EG0020 events0 affected13 at risk EG003
Fatigue	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected15 at risk EG0020 events0 affected13 at risk EG003
Traumatic Ulcer	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected15 at risk EG0020 events0 affected13 at risk EG003

ID	Term
D003924	Diabetes Mellitus, Type 2
D010188	Exocrine Pancreatic Insufficiency

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D010182	Pancreatic Diseases
D004066	Digestive System Diseases

ID	Title	Description
BG000	Low FEC (EPANOVA® and OMACOR®)	Patients had low levels (<100 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function.
BG001	Intermediate FEC (EPANOVA® and OMACOR®)	Patients had intermediate levels (≥100 to <200 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function.
BG002	Normal FEC (EPANOVA® and OMACOR®)	Patients had normal levels (≥200 mcg/g) of FEC, as determined by the average of the FEC from 2 stool samples collected between Visit 2 and Visit 3 as a measure of pancreatic exocrine function.
BG003	Total	Total of all reporting groups