Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35236   clinical trials with a EudraCT protocol, of which   5759   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Two-part, Open-label, Randomised, Crossover, Multicentre, Phase II Study to Investigate the Presence of Pancreatic Exocrine Insufficiency (PEI) in Patients with Type 2 Diabetes Mellitus, and to Investigate the Pharmacokinetics of EPANOVA® and OMACOR® Following a Single Oral Dose in Patients with Different Degrees of PEI

    Summary
    EudraCT number
    2014-003511-11
    Trial protocol
    SK   SE   DK   HU   LV   PL  
    Global end of trial date
    17 Nov 2015

    Results information
    Results version number
    v2(current)
    This version publication date
    22 Dec 2016
    First version publication date
    29 Sep 2016
    Other versions
    v1
    Version creation reason

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    D5881C00006
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02370537
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    Gärturnavägen 1, Södertälje, Sweden, SE-151 85
    Public contact
    Stefan Carlsson, AstraZeneca AB, Stefan.C.Carlsson@astrazeneca.com
    Scientific contact
    Stefan Carlsson, AstraZeneca AB, Stefan.C.Carlsson@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Nov 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    17 Nov 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Nov 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    In Part A, to describe the distribution of serum triglycerides (TGs) in patients with Type 2 Diabetes Mellitus (T2DM) by degree of PEI as determined by levels of faecal elastase-1 concentrations (FEC). In Part B, to evaluate and compare the plasma exposure of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from EPANOVA® and OMACOR®, respectively, in patients with T2DM with different levels of FEC.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice and applicable regulatory requirements and the AstraZeneca policy on Bioethics.
    Background therapy
    -
    Evidence for comparator
    OMACOR® is an omega-3 fatty acid ethyl esters formulation that is approved treatment for the same indication as EPANOVA®, i.e. as an adjunct to diet to reduce TG levels in adults with severe hypertriglyceridaemia and is used as a comparator in this study. OMACOR® requires hydrolysis in the small intestine by pancreatic lipase for intestinal absorption whereas EPANOVA® does not.
    Actual start date of recruitment
    07 Apr 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Denmark: 25
    Country: Number of subjects enrolled
    Hungary: 83
    Country: Number of subjects enrolled
    Latvia: 68
    Country: Number of subjects enrolled
    Poland: 45
    Country: Number of subjects enrolled
    Slovakia: 14
    Country: Number of subjects enrolled
    Sweden: 80
    Worldwide total number of subjects
    315
    EEA total number of subjects
    315
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    193
    From 65 to 84 years
    122
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    First patient enrolled: 7 April 2015. Last patient completed Part B: 17 November 2015. This study was performed in 23 centres across 6 countries in Europe.

    Pre-assignment
    Screening details
    A total of 490 patients were screened and of these, 315 patients met all inclusion and none of the exclusion criteria and completed the first part of the study. 51 patients were randomised to treatment in the second part of the study.

    Period 1
    Period 1 title
    Part A (Open-label recruitment)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Low FEC (EPANOVA® and OMACOR®)
    Arm description
    Part A investigated serum lipids, especially TGs and 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).
    Arm type
    Stratum of pancreatic exocrine function

    Investigational medicinal product name
    EPANOVA®
    Investigational medicinal product code
    Other name
    Omega-3 carboxylic acids
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a Therapeutic Lifestyle Changes (TLC) diet-based breakfast.

    Investigational medicinal product name
    OMACOR®
    Investigational medicinal product code
    Other name
    Omega-3 ethyl ester
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Arm title
    Intermediate FEC (EPANOVA® and OMACOR®)
    Arm description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).
    Arm type
    Stratum of pancreatic exocrine function

    Investigational medicinal product name
    EPANOVA®
    Investigational medicinal product code
    Other name
    Omega-3 carboxylic acids
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Investigational medicinal product name
    OMACOR®
    Investigational medicinal product code
    Other name
    Omega-3 ethyl ester
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Arm title
    Normal FEC (EPANOVA® and OMACOR®)
    Arm description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).
    Arm type
    Stratum of pancreatic exocrine function

    Investigational medicinal product name
    EPANOVA®
    Investigational medicinal product code
    Other name
    Omega-3 carboxylic acids
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Investigational medicinal product name
    OMACOR®
    Investigational medicinal product code
    Other name
    Omega-3 ethyl ester
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Number of subjects in period 1
    Low FEC (EPANOVA® and OMACOR®) Intermediate FEC (EPANOVA® and OMACOR®) Normal FEC (EPANOVA® and OMACOR®)
    Started
    16
    16
    283
    Completed
    16
    15
    282
    Not completed
    0
    1
    1
         Adverse event, non-fatal
             -
             -
             1
         Consent withdrawn by subject
             -
             1
             -
    Period 2
    Period 2 title
    Part B
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Low FEC (EPANOVA® and OMACOR®)
    Arm description
    Part A investigated serum lipids, especially TGs and 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 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).
    Arm type
    Stratum of pancreatic exocrine function

    Investigational medicinal product name
    EPANOVA®
    Investigational medicinal product code
    Other name
    Omega-3 carboxylic acids
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Investigational medicinal product name
    OMACOR®
    Investigational medicinal product code
    Other name
    Omega-3 ethyl ester
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Arm title
    Intermediate FEC (EPANOVA® and OMACOR®)
    Arm description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).
    Arm type
    Stratum of pancreatic exocrine function

    Investigational medicinal product name
    OMACOR®
    Investigational medicinal product code
    Other name
    Omega-3 ethyl ester
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Investigational medicinal product name
    EPANOVA®
    Investigational medicinal product code
    Other name
    Omega-3 carboxylic acids
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Arm title
    Normal FEC (EPANOVA® and OMACOR®)
    Arm description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).
    Arm type
    Stratum of pancreatic exocrine function

    Investigational medicinal product name
    OMACOR®
    Investigational medicinal product code
    Other name
    Omega-3 ethyl ester
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Investigational medicinal product name
    EPANOVA®
    Investigational medicinal product code
    Other name
    Omega-3 carboxylic acids
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) was taken orally 30 minutes after the start of a TLC diet-based breakfast.

    Number of subjects in period 2
    Low FEC (EPANOVA® and OMACOR®) Intermediate FEC (EPANOVA® and OMACOR®) Normal FEC (EPANOVA® and OMACOR®)
    Started
    16
    15
    282
    Randomised in Part B
    15
    13
    23
    Period 1 Sequence AB
    8 [1]
    6 [2]
    11 [3]
    Period 1 Sequence BA
    7 [4]
    7 [5]
    12 [6]
    Period 2 Sequence AB
    8 [7]
    5 [8]
    11 [9]
    Period 2 Sequence BA
    7 [10]
    7 [11]
    12 [12]
    Completed
    15
    12
    23
    Not completed
    1
    3
    259
         Not randomised to receive treatment
             1
             2
             259
         Consent withdrawn by subject
             -
             1
             -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.
    [12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects started and completed is presented for Period 2 (Part B) overall; additionally the intermediate milestones represent the numbers of subjects completing each treatment sequence.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Low FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and 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).

    Reporting group title
    Intermediate FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).

    Reporting group title
    Normal FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).

    Reporting group values
    Low FEC (EPANOVA® and OMACOR®) Intermediate FEC (EPANOVA® and OMACOR®) Normal FEC (EPANOVA® and OMACOR®) Total
    Number of subjects
    16 16 283 315
    Age categorical
    Units: Subjects
        In Utero
    0 0 0 0
        Preterm newborn- gestational age < 37 weeks
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days - 23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        From 18 - 64 years
    11 11 171 193
        From 65 - 84 years
    5 5 112 122
        Over 85 years
    0 0 0 0
    Gender, Male/Female
    Units: Participants
        Female
    5 5 123 133
        Male
    11 11 160 182

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Low FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and 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).

    Reporting group title
    Intermediate FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).

    Reporting group title
    Normal FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).
    Reporting group title
    Low FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and 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 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).

    Reporting group title
    Intermediate FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).

    Reporting group title
    Normal FEC (EPANOVA® and OMACOR®)
    Reporting group description
    Part A investigated serum lipids, especially TGs and FEC as a measure of pancreatic exocrine function 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. 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).

    Subject analysis set title
    Low FEC (EPANOVA® and OMACOR®)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    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.

    Subject analysis set title
    Intermediate FEC (EPANOVA® and OMACOR®)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    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.

    Subject analysis set title
    Normal FEC (EPANOVA® and OMACOR®)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    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.

    Subject analysis set title
    Low FEC (EPANOVA® and OMACOR®)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    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.

    Subject analysis set title
    Intermediate FEC (EPANOVA® and OMACOR®)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    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.

    Subject analysis set title
    Normal FEC (EPANOVA® and OMACOR®)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    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.

    Subject analysis set title
    Low FEC (EPANOVA®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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).

    Subject analysis set title
    Low FEC (OMACOR®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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).

    Subject analysis set title
    Intermediate FEC (EPANOVA®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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 intermediate FEC, ≥ 100 to <200 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).

    Subject analysis set title
    Intermediate FEC (OMACOR®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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 intermediate FEC, ≥ 100 to <200 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).

    Subject analysis set title
    Normal FEC (EPANOVA®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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 normal FEC, ≥ 200 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).

    Subject analysis set title
    Normal FEC (OMACOR®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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 normal FEC, ≥ 200 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).

    Subject analysis set title
    Low FEC (OMACOR®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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).

    Subject analysis set title
    Normal FEC (EPANOVA®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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 normal FEC, ≥ 200 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).

    Subject analysis set title
    Normal FEC (OMACOR®)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    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 normal FEC, ≥ 200 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 A: Serum TG level.

    Close Top of page
    End point title
    Part A: Serum TG level. [1]
    End point description
    For Part A, the distribution of serum TG levels by the degree of PEI was assessed in patients with T2DM. Data is presented for the Per Protocol Analysis Set which included all enrolled patients without an important protocol deviation.
    End point type
    Primary
    End point timeframe
    7 days after enrollment.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analysis was planned and performed for the variables in Part A.
    End point values
    Low FEC (EPANOVA® and OMACOR®) Intermediate FEC (EPANOVA® and OMACOR®) Normal FEC (EPANOVA® and OMACOR®)
    Number of subjects analysed
    15
    16
    278
    Units: millimole per litre (mmol/L)
        arithmetic mean (standard deviation)
    2.07 ± 0.63
    1.68 ± 0.57
    2 ± 1.16
    No statistical analyses for this end point

    Primary: Part B: Baseline corrected area under the plasma concentration time curve from time zero to last measurable concentration (AUC[0-last]) for total EPA following administration of EPANOVA® and OMACOR®.

    Close Top of page
    End point title
    Part B: Baseline corrected area under the plasma concentration time curve from time zero to last measurable concentration (AUC[0-last]) for total EPA following administration of EPANOVA® and OMACOR®.
    End point description
    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. Data is presented for the Pharmacokinetic (PK) Analysis Set which 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.
    End point type
    Primary
    End point timeframe
    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.
    End point values
    Low FEC (EPANOVA®) Low FEC (OMACOR®) Intermediate FEC (EPANOVA®) Intermediate FEC (OMACOR®) Normal FEC (EPANOVA®) Normal FEC (OMACOR®)
    Number of subjects analysed
    15
    14
    13
    12
    21
    22
    Units: hours*mcg per millilitre (h*mcg/mL)
        geometric mean (geometric coefficient of variation)
    2170 ± 65.2
    1650 ± 31.3
    2000 ± 82.8
    946 ± 96
    2070 ± 36.1
    1260 ± 126
    Statistical analysis title
    OMACOR® v EPANOVA® for low FEC group
    Statistical analysis description
    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.
    Comparison groups
    Low FEC (EPANOVA®) v Low FEC (OMACOR®)
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    [2]
    Method
    Parameter type
    Geometric least-squares (GLS) Mean Ratio
    Point estimate
    0.75
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.52
         upper limit
    1.1
    Notes
    [2] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for intermediate FEC group
    Statistical analysis description
    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.
    Comparison groups
    Intermediate FEC (EPANOVA®) v Intermediate FEC (OMACOR®)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    [3]
    Method
    Parameter type
    GLS Mean ratio
    Point estimate
    0.48
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.32
         upper limit
    0.72
    Notes
    [3] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for normal FEC group
    Statistical analysis description
    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.
    Comparison groups
    Normal FEC (EPANOVA®) v Normal FEC (OMACOR®)
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    [4]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.44
         upper limit
    0.82
    Notes
    [4] - 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.

    Primary: Part B: Baseline corrected AUC(0-last) for total DHA following administration of EPANOVA® and OMACOR®.

    Close Top of page
    End point title
    Part B: Baseline corrected AUC(0-last) for total DHA following administration of EPANOVA® and OMACOR®.
    End point description
    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. Data is presented for the PK Analysis Set which 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.
    End point type
    Primary
    End point timeframe
    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.
    End point values
    Low FEC (EPANOVA®) Low FEC (OMACOR®) Intermediate FEC (EPANOVA®) Intermediate FEC (OMACOR®) Normal FEC (EPANOVA®) Normal FEC (OMACOR®)
    Number of subjects analysed
    15
    14
    13
    12
    21
    22
    Units: h*mcg/mL
        geometric mean (geometric coefficient of variation)
    801 ± 55.7
    1040 ± 47.1
    719 ± 85
    567 ± 70.7
    625 ± 90.2
    810 ± 105
    Statistical analysis title
    OMACOR® v EPANOVA® for low FEC group
    Statistical analysis description
    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.
    Comparison groups
    Low FEC (EPANOVA®) v Low FEC (OMACOR®)
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    [5]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    1.28
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    1.93
    Notes
    [5] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for intermediate FEC group
    Statistical analysis description
    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.
    Comparison groups
    Intermediate FEC (EPANOVA®) v Intermediate FEC (OMACOR®)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    [6]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.8
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.51
         upper limit
    1.25
    Notes
    [6] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for normal FEC group
    Statistical analysis description
    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.
    Comparison groups
    Normal FEC (EPANOVA®) v Normal FEC (OMACOR®)
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    [7]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    1.29
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.92
         upper limit
    1.82
    Notes
    [7] - 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.

    Primary: Part B: Baseline corrected AUC(0-last) for total EPA+DHA following administration of EPANOVA® and OMACOR®.

    Close Top of page
    End point title
    Part B: Baseline corrected AUC(0-last) for total EPA+DHA following administration of EPANOVA® and OMACOR®.
    End point description
    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. Data is presented for the PK Analysis Set which 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.
    End point type
    Primary
    End point timeframe
    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.
    End point values
    Low FEC (EPANOVA®) Low FEC (OMACOR®) Intermediate FEC (EPANOVA®) Intermediate FEC (OMACOR®) Normal FEC (EPANOVA®) Normal FEC (OMACOR®)
    Number of subjects analysed
    15
    14
    13
    12
    21
    22
    Units: h*nanomole/mL (h*nmol/mL)
        geometric mean (geometric coefficient of variation)
    9700 ± 57.7
    8780 ± 32.9
    8990 ± 72.4
    5130 ± 80.6
    8890 ± 43.8
    6690 ± 112
    Statistical analysis title
    OMACOR® v EPANOVA® for low FEC group
    Statistical analysis description
    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.
    Comparison groups
    Low FEC (EPANOVA®) v Low FEC (OMACOR®)
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    [8]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.9
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.63
         upper limit
    1.28
    Notes
    [8] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for intermediate FEC group
    Statistical analysis description
    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.
    Comparison groups
    Intermediate FEC (EPANOVA®) v Intermediate FEC (OMACOR®)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    [9]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.58
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.39
         upper limit
    0.85
    Notes
    [9] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for normal FEC group
    Statistical analysis description
    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.
    Comparison groups
    Normal FEC (EPANOVA®) v Normal FEC (OMACOR®)
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    [10]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.75
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.55
         upper limit
    1
    Notes
    [10] - 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.

    Primary: Part B: Baseline corrected maximum plasma drug concentration (Cmax) for total EPA following administration of EPANOVA® and OMACOR®.

    Close Top of page
    End point title
    Part B: Baseline corrected maximum plasma drug concentration (Cmax) for total EPA following administration of EPANOVA® and OMACOR®.
    End point description
    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. Data is presented for the PK Analysis Set which 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.
    End point type
    Primary
    End point timeframe
    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.
    End point values
    Low FEC (EPANOVA®) Intermediate FEC (EPANOVA®) Intermediate FEC (OMACOR®) Low FEC (OMACOR®) Normal FEC (EPANOVA®) Normal FEC (OMACOR®)
    Number of subjects analysed
    15
    13
    12
    15
    22
    23
    Units: mcg/mL
        geometric mean (geometric coefficient of variation)
    137 ± 70.5
    116 ± 53.3
    53.9 ± 70.1
    71.5 ± 64
    131 ± 36.2
    69.3 ± 76.2
    Statistical analysis title
    OMACOR® v EPANOVA® for low FEC group
    Statistical analysis description
    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.
    Comparison groups
    Low FEC (OMACOR®) v Low FEC (EPANOVA®)
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    [11]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.52
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.37
         upper limit
    0.73
    Notes
    [11] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for intermediate FEC group
    Statistical analysis description
    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.
    Comparison groups
    Intermediate FEC (EPANOVA®) v Intermediate FEC (OMACOR®)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    [12]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.46
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.32
         upper limit
    0.67
    Notes
    [12] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for normal FEC group
    Statistical analysis description
    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.
    Comparison groups
    Normal FEC (EPANOVA®) v Normal FEC (OMACOR®)
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    [13]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.53
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    0.7
    Notes
    [13] - 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.

    Primary: Part B: Baseline corrected Cmax for total DHA following administration of EPANOVA® and OMACOR®.

    Close Top of page
    End point title
    Part B: Baseline corrected Cmax for total DHA following administration of EPANOVA® and OMACOR®.
    End point description
    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. Data is presented for the PK Analysis Set which 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.
    End point type
    Primary
    End point timeframe
    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.
    End point values
    Low FEC (EPANOVA®) Intermediate FEC (EPANOVA®) Intermediate FEC (OMACOR®) Low FEC (OMACOR®) Normal FEC (EPANOVA®) Normal FEC (OMACOR®)
    Number of subjects analysed
    15
    13
    12
    15
    22
    23
    Units: mcg/mL
        geometric mean (geometric coefficient of variation)
    59 ± 58.6
    56 ± 40.6
    51 ± 52
    60.5 ± 47.3
    53.8 ± 41.8
    59.7 ± 53.9
    Statistical analysis title
    OMACOR® v EPANOVA® for low FEC group
    Statistical analysis description
    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.
    Comparison groups
    Low FEC (EPANOVA®) v Low FEC (OMACOR®)
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    [14]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    1.02
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.77
         upper limit
    1.36
    Notes
    [14] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for normal FEC group
    Statistical analysis description
    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.
    Comparison groups
    Normal FEC (EPANOVA®) v Normal FEC (OMACOR®)
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    [15]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    1.11
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.88
         upper limit
    1.4
    Notes
    [15] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for intermediate FEC
    Statistical analysis description
    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.
    Comparison groups
    Intermediate FEC (EPANOVA®) v Intermediate FEC (OMACOR®)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    [16]
    Method
    Parameter type
    GLS mean Ratio
    Point estimate
    0.92
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.67
         upper limit
    1.25
    Notes
    [16] - 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.

    Primary: Part B: Baseline corrected Cmax for total EPA+DHA following administration of EPANOVA® and OMACOR®.

    Close Top of page
    End point title
    Part B: Baseline corrected Cmax for total EPA+DHA following administration of EPANOVA® and OMACOR®.
    End point description
    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. Data is presented for the PK Analysis Set which 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.
    End point type
    Primary
    End point timeframe
    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.
    End point values
    Low FEC (EPANOVA®) Intermediate FEC (EPANOVA®) Intermediate FEC (OMACOR®) Low FEC (OMACOR®) Normal FEC (EPANOVA®) Normal FEC (OMACOR®)
    Number of subjects analysed
    15
    13
    12
    15
    22
    23
    Units: nmol/mL
        geometric mean (geometric coefficient of variation)
    622 ± 69.7
    553 ± 47
    328 ± 57.2
    421 ± 54
    592 ± 36.6
    413 ± 61.7
    Statistical analysis title
    OMACOR® v EPANOVA® for low FEC group
    Statistical analysis description
    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.
    Comparison groups
    Low FEC (EPANOVA®) v Low FEC (OMACOR®)
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    [17]
    Method
    Parameter type
    GLS Mean
    Point estimate
    0.68
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.49
         upper limit
    0.92
    Notes
    [17] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for intermediate FEC group
    Statistical analysis description
    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.
    Comparison groups
    Intermediate FEC (EPANOVA®) v Intermediate FEC (OMACOR®)
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    [18]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.42
         upper limit
    0.84
    Notes
    [18] - 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.
    Statistical analysis title
    OMACOR® v EPANOVA® for normal FEC group
    Statistical analysis description
    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.
    Comparison groups
    Normal FEC (EPANOVA®) v Normal FEC (OMACOR®)
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    [19]
    Method
    Parameter type
    GLS Mean Ratio
    Point estimate
    0.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.54
         upper limit
    0.9
    Notes
    [19] - 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.

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All adverse events (AEs) were collected until the safety follow-up contact (Visit 10). Serious AEs were collected from Visit 1 (screening) onwards over a period of up to 13 weeks. Other AEs were recorded from Visit 2 over a period of 7 weeks.
    Adverse event reporting additional description
    Regular investigator assessment at study sites. Population used was the Safety Analysis Set which included all patients who received at least 1 dose of study treatment in Part B.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Low FEC (EPANOVA®)
    Reporting group description
    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.

    Reporting group title
    Low FEC (OMACOR®)
    Reporting group description
    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.

    Reporting group title
    Intermediate FEC (EPANOVA®)
    Reporting group description
    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.

    Reporting group title
    Intermediate FEC (OMACOR®)
    Reporting group description
    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.

    Reporting group title
    Normal FEC (EPANOVA®)
    Reporting group description
    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.

    Reporting group title
    Normal FEC (OMACOR®)
    Reporting group description
    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.

    Serious adverse events
    Low FEC (EPANOVA®) Low FEC (OMACOR®) Intermediate FEC (EPANOVA®) Intermediate FEC (OMACOR®) Normal FEC (EPANOVA®) Normal FEC (OMACOR®)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 23 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 23 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Low FEC (EPANOVA®) Low FEC (OMACOR®) Intermediate FEC (EPANOVA®) Intermediate FEC (OMACOR®) Normal FEC (EPANOVA®) Normal FEC (OMACOR®)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    5 / 23 (21.74%)
    1 / 23 (4.35%)
    Injury, poisoning and procedural complications
    Traumatic Ulcer
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    2 / 23 (8.70%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Abdominal Pain
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Dry Mouth
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Flatulence
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 23 (4.35%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 23 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA