Diabetes Mellitus, Type 2, Exocrine Pancreatic Insufficiency
Conditions
Keywords
omega-3 carboxylic acid
Brief summary
This study is a 2-part open-label, randomized, crossover, multicenter, non-therapeutic Phase II study to investigate the presence of pancreatic exocrine insufficiency (PEI) in patients with Type 2 diabetes mellitus (T2DM), and to investigate the pharmacokinetics (PK) of EPANOVA® (omega-3 carboxylic acids) and omega-3-acid ethyl esters (OMACOR®, Abbott Healthcare Products Ltd) following a single oral dose in patients with different degrees of PEI.
Interventions
4 g (administered orally as 4 x 1 g capsules)
DRUGOmacor® (omega-3-acid ethyl esters)
4 g (administered orally as 4 x 1 g capsules)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female aged ≥18 years and ≤70 years, with suitable veins for cannulation or repeated venipuncture. * Clinically diagnosed Type 2 diabetics (American Diabetes Association guidelines;), on oral antibiotic drug use ≥3 months and HbA1c value ≥6.5% and ≤9.0% at Visit 1. * Have a body mass index ≥18 kg/m2 and ≤40 kg/m2 and weigh at least 50 kg.
Exclusion criteria
* Intolerance to Omega-3 fatty acids, ethyl esters or fish. * On insulin therapy or treated with injectable Glucagon-like peptide-1 (GLP-1). * Treated with bile acid sequestrants. * Serum levels of TGs \>10 mmol/L at any time during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Serum TG Level. | 7 days after enrollment. | 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). |
| 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®. | 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. | 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. |
| Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®. | 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. | 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. |
| Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 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. | 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. |
| Part B: Baseline Corrected Maximum Plasma Drug Concentration (Cmax) for Total EPA Following Administration of EPANOVA® and OMACOR®. | 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. | 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. |
| Part B: Baseline Corrected Cmax for Total DHA Following Administration of EPANOVA® and OMACOR®. | 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. | 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. |
| Part B: Baseline Corrected Cmax for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 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. | 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. |
Countries
Denmark, Hungary, Latvia, Poland, Slovakia, Sweden
Participant flow
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 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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 16 |
| 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. | 16 |
| 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. | 283 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A (Open-label Recruitment) | Adverse Event | 0 | 0 | 1 |
| Part A (Open-label Recruitment) | Withdrawal by Subject | 0 | 1 | 0 |
| Part B | Not randomised to receive treatment | 1 | 2 | 259 |
| Part B | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Low FEC (EPANOVA® and OMACOR®) | Intermediate FEC (EPANOVA® and OMACOR®) | Normal FEC (EPANOVA® and OMACOR®) | Total |
|---|---|---|---|---|
| Age, Customized From 18 - 64 years | 11 Participants | 11 Participants | 171 Participants | 193 Participants |
| Age, Customized From 65 - 84 years | 5 Participants | 5 Participants | 112 Participants | 122 Participants |
| Age, Customized Over 85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 5 Participants | 5 Participants | 123 Participants | 133 Participants |
| Gender Male | 11 Participants | 11 Participants | 160 Participants | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 15 | 1 / 15 | 0 / 13 | 0 / 12 | 5 / 23 | 1 / 23 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 13 | 1 / 12 | 0 / 23 | 0 / 23 |
Outcome results
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).
Time frame: 7 days after enrollment.
Population: The Per Protocol Analysis Set included all enrolled patients without an important protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low FEC (EPANOVA® and OMACOR®) | Part A: Serum TG Level. | 2.07 millimole per litre (mmol/L) | Standard Deviation 0.63 |
| Intermediate FEC (EPANOVA® and OMACOR®) | Part A: Serum TG Level. | 1.68 millimole per litre (mmol/L) | Standard Deviation 0.57 |
| Normal FEC (EPANOVA® and OMACOR®) | Part A: Serum TG Level. | 2.00 millimole per litre (mmol/L) | Standard Deviation 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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Low FEC (EPANOVA® and OMACOR®) | 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®. | 2170 hours*mcg per millilitre (h*mcg/mL) | Geometric Coefficient of Variation 65.2 |
| Intermediate FEC (EPANOVA® and OMACOR®) | 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®. | 1650 hours*mcg per millilitre (h*mcg/mL) | Geometric Coefficient of Variation 31.3 |
| Normal FEC (EPANOVA® and OMACOR®) | 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®. | 2000 hours*mcg per millilitre (h*mcg/mL) | Geometric Coefficient of Variation 82.8 |
| Intermediate FEC (OMACOR®) | 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®. | 946 hours*mcg per millilitre (h*mcg/mL) | Geometric Coefficient of Variation 96 |
| Normal FEC (EPANOVA®) | 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®. | 2070 hours*mcg per millilitre (h*mcg/mL) | Geometric Coefficient of Variation 36.1 |
| Normal FEC (OMACOR®) | 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®. | 1260 hours*mcg per millilitre (h*mcg/mL) | Geometric Coefficient of Variation 126 |
Comparison: 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.90% CI: [0.52, 1.1]
Comparison: 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.90% CI: [0.32, 0.72]
Comparison: 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.90% CI: [0.44, 0.82]
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Low FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®. | 801 h*mcg/mL | Geometric Coefficient of Variation 55.7 |
| Intermediate FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®. | 1040 h*mcg/mL | Geometric Coefficient of Variation 47.1 |
| Normal FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®. | 719 h*mcg/mL | Geometric Coefficient of Variation 85 |
| Intermediate FEC (OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®. | 567 h*mcg/mL | Geometric Coefficient of Variation 70.7 |
| Normal FEC (EPANOVA®) | Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®. | 625 h*mcg/mL | Geometric Coefficient of Variation 90.2 |
| Normal FEC (OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total Docosahexaenoic Acid (DHA) Following Administration of EPANOVA® and OMACOR®. | 810 h*mcg/mL | Geometric Coefficient of Variation 105 |
Comparison: 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.90% CI: [0.84, 1.93]
Comparison: 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.90% CI: [0.51, 1.25]
Comparison: 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.90% CI: [0.92, 1.82]
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Low FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 9700 h*nanomole/mL (h*nmol/mL) | Geometric Coefficient of Variation 57.7 |
| Intermediate FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 8780 h*nanomole/mL (h*nmol/mL) | Geometric Coefficient of Variation 32.9 |
| Normal FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 8990 h*nanomole/mL (h*nmol/mL) | Geometric Coefficient of Variation 72.4 |
| Intermediate FEC (OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 5130 h*nanomole/mL (h*nmol/mL) | Geometric Coefficient of Variation 80.6 |
| Normal FEC (EPANOVA®) | Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 8890 h*nanomole/mL (h*nmol/mL) | Geometric Coefficient of Variation 43.8 |
| Normal FEC (OMACOR®) | Part B: Baseline Corrected AUC(0-last) for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 6690 h*nanomole/mL (h*nmol/mL) | Geometric Coefficient of Variation 112 |
Comparison: 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.90% CI: [0.63, 1.28]
Comparison: 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.90% CI: [0.39, 0.85]
Comparison: 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.90% CI: [0.55, 1]
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Low FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Cmax for Total DHA Following Administration of EPANOVA® and OMACOR®. | 59.0 mcg/mL | Geometric Coefficient of Variation 58.6 |
| Intermediate FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Cmax for Total DHA Following Administration of EPANOVA® and OMACOR®. | 60.5 mcg/mL | Geometric Coefficient of Variation 47.3 |
| Normal FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Cmax for Total DHA Following Administration of EPANOVA® and OMACOR®. | 56.0 mcg/mL | Geometric Coefficient of Variation 40.6 |
| Intermediate FEC (OMACOR®) | Part B: Baseline Corrected Cmax for Total DHA Following Administration of EPANOVA® and OMACOR®. | 51.0 mcg/mL | Geometric Coefficient of Variation 52 |
| Normal FEC (EPANOVA®) | Part B: Baseline Corrected Cmax for Total DHA Following Administration of EPANOVA® and OMACOR®. | 53.8 mcg/mL | Geometric Coefficient of Variation 41.8 |
| Normal FEC (OMACOR®) | Part B: Baseline Corrected Cmax for Total DHA Following Administration of EPANOVA® and OMACOR®. | 59.7 mcg/mL | Geometric Coefficient of Variation 53.9 |
Comparison: 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.90% CI: [0.77, 1.36]
Comparison: 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.90% CI: [0.67, 1.25]
Comparison: 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.90% CI: [0.88, 1.4]
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Low FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Cmax for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 622 nmol/mL | Geometric Coefficient of Variation 69.7 |
| Intermediate FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Cmax for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 421 nmol/mL | Geometric Coefficient of Variation 54 |
| Normal FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Cmax for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 553 nmol/mL | Geometric Coefficient of Variation 47 |
| Intermediate FEC (OMACOR®) | Part B: Baseline Corrected Cmax for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 328 nmol/mL | Geometric Coefficient of Variation 57.2 |
| Normal FEC (EPANOVA®) | Part B: Baseline Corrected Cmax for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 592 nmol/mL | Geometric Coefficient of Variation 36.6 |
| Normal FEC (OMACOR®) | Part B: Baseline Corrected Cmax for Total EPA+DHA Following Administration of EPANOVA® and OMACOR®. | 413 nmol/mL | Geometric Coefficient of Variation 61.7 |
Comparison: 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.90% CI: [0.49, 0.92]
Comparison: 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.90% CI: [0.42, 0.84]
Comparison: 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.90% CI: [0.54, 0.9]
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Low FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Maximum Plasma Drug Concentration (Cmax) for Total EPA Following Administration of EPANOVA® and OMACOR®. | 137 mcg/mL | Geometric Coefficient of Variation 70.5 |
| Intermediate FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Maximum Plasma Drug Concentration (Cmax) for Total EPA Following Administration of EPANOVA® and OMACOR®. | 71.5 mcg/mL | Geometric Coefficient of Variation 64 |
| Normal FEC (EPANOVA® and OMACOR®) | Part B: Baseline Corrected Maximum Plasma Drug Concentration (Cmax) for Total EPA Following Administration of EPANOVA® and OMACOR®. | 116 mcg/mL | Geometric Coefficient of Variation 53.3 |
| Intermediate FEC (OMACOR®) | Part B: Baseline Corrected Maximum Plasma Drug Concentration (Cmax) for Total EPA Following Administration of EPANOVA® and OMACOR®. | 53.9 mcg/mL | Geometric Coefficient of Variation 70.1 |
| Normal FEC (EPANOVA®) | Part B: Baseline Corrected Maximum Plasma Drug Concentration (Cmax) for Total EPA Following Administration of EPANOVA® and OMACOR®. | 131 mcg/mL | Geometric Coefficient of Variation 36.2 |
| Normal FEC (OMACOR®) | Part B: Baseline Corrected Maximum Plasma Drug Concentration (Cmax) for Total EPA Following Administration of EPANOVA® and OMACOR®. | 69.3 mcg/mL | Geometric Coefficient of Variation 76.2 |
Comparison: 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.90% CI: [0.37, 0.73]
Comparison: 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.90% CI: [0.32, 0.67]
Comparison: 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.90% CI: [0.4, 0.7]