A Study to Investigate How Common Pancreatic Exocrine Insufficiency (PEI) is in Patients With Type 2 Diabetes and Also to Investigate the Uptake of a Single Dose of EPANOVA® or OMACOR® in Patients With Different Degrees of PEI

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Diabetes Mellitus, Type 2, Exocrine Pancreatic Insufficiency

Intervention / Treatment
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* Drug: Epanova® (omega-3 carboxylic acids)
* Drug: Omacor® (omega-3-acid ethyl esters)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence AB<br>A single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) at Visit 4, followed by 10 to 14 days washout, followed by a single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) at Visit 7. | Drug: Epanova® (omega-3 carboxylic acids)<br>* 4 g (administered orally as 4 x 1 g capsules)<br>* Other names: omega-3 carboxylic acids;Drug: Omacor® (omega-3-acid ethyl esters)<br>* 4 g (administered orally as 4 x 1 g capsules)<br>* Other names: omega-3-acid ethyl esters;|
| Experimental: Sequence BA<br>A single dose of OMACOR® 4 g (administered as 4 x 1 g capsules) at Visit 4, followed by 10 to 14 days washout, followed by a single dose of EPANOVA® 4 g (administered as 4 x 1 g capsules) at Visit 7. | Drug: Epanova® (omega-3 carboxylic acids)<br>* 4 g (administered orally as 4 x 1 g capsules)<br>* Other names: omega-3 carboxylic acids;Drug: Omacor® (omega-3-acid ethyl esters)<br>* 4 g (administered orally as 4 x 1 g capsules)<br>* Other names: omega-3-acid ethyl esters;|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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omega-3 carboxylic acid