E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of Part A of the trial is to describe the distribution of plasma triglycerides in patients with Type 2 Diabetes Mellitus by degree of pancreatic exocrine insufficiency (Normal: faecal elastase-1 concentration [FEC] ≥200 μg/g; Intermediate: FEC ≥100 μg/g to <200 μg/g; and Low: FEC <100 μg/g). The primary objective of Part B of the trial is to evaluate and compare the plasma exposure of docosahexaenoic acid and eicosapentaenoic acid from EPANOVA® and OMACOR®, respectively, in patients with Type 2 Diabetes Mellitus with different levels of FEC. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female aged ≥18 years and ≤70 years, with suitable veins for cannulation or repeated venipuncture.
2. Clinically diagnosed Type 2 diabetics (American Diabetes Association guidelines; American Diabetes Association 2014), on oral antidiabetic drug use ≥3 months and HbA1c value ≥6.5% and ≤9.0% at Visit 1.
3. Have a body mass index ≥18 kg/m2 and ≤40 kg/m2 and weigh at least 50 kg.
4. Be willing to maintain current activity level.
5. For patients on treatment for hypertriglyceridaemia: be willing to stop treatment with fibrates, niacin and Omega-3 at Visit 1 and for the duration of the entire study.
6. Be willing to adhere to the total fat intake recommended by the Therapeutic Lifestyle Changes diet during screening and washout periods.
7. Be willing to avoid consuming fish, seafood and fish products from Visit 2 and for the remainder of the study. |
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E.4 | Principal exclusion criteria |
1. History of, or presence of (as found at Visit 1) any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient’s ability to participate in the study.
2. Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of the first administration of IP.
3. Intolerance to Omega-3 fatty acids, ethyl esters or fish.
4. On insulin therapy or treated with injectable glucagon-like peptide-1.
5. Treated with bile acid sequestrants.
6. Use of fish oil, other eicosapentaenoic acid or docosahexaenoic acid-containing supplements, or eicosapentaenoic acid and/or docosahexaenoic acid-fortified foods within 4 weeks of Visit 2, or during the study.
7. Use of flaxseed, perilla seed, hemp, spirulina, or blackcurrant oils within 7 days of Visit 2, and during the remainder of the study.
8. Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the Investigator, found at Visit 1.
9. Plasma levels of triglycerides >10 mmol/L at any time during the study:
− Plasma levels of triglycerides will be checked at enrolment (Visit 2). Results should be available prior to any further study-related procedures being performed.
10. Smokers who cannot abstain from smoking during the clinic visits.
11. Recent history (past 12 months) of drug abuse or alcohol abuse, as judged by the Investigator.
12. Women who are pregnant, lactating, or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is <1 year since last menstrual period.
13. Any other condition the Investigator believes would interfere with the patient’s ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the patient at undue risk.
14. Plasma donation within one month of screening or any blood donation/blood loss >500 mL during the 3 months prior to Visit 2 or during the study.
15. Ongoing substitution therapy with pancreatic enzymes. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measures for Part A are plasma triglyceride levels and faecal elastase-1 concentration at the end of Part A. The primary outcome measures for Part B are baseline-corrected area under plasma concentration time curve from time 0 to the last measurable
concentration (AUC0-t), area under plasma concentration-time curve from zero to infinity (AUC)
and maximum plasma drug concentration (Cmax) of the sum of DHA+EPA, and EPA and DHA
separately, during Part B. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part A: Day 7±2 days; Part B: Visit 4 (Day 21) and Visit 7 (10-14 days after Visit 4): 1, 2, 3, 4, 5, 6, 7, 8 and 10 hours after dosing; Visit 5 (1 day after Visit 4), Visit 6 (2 days after Visit 4), Visit 8 (1 day after Visit 7), and Visit 9 (2 days after Visit 7): 24 and 48 hours after dosing. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |