E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The project deals with hummoral and metabolic aspects of insulin resistance (IR), which is assumed to be the basic metabolic disorder which leads to the development of type 2 diabetes mellitus (T2D) and metabolic syndrome. Study population will be patients with T2D treated by metformin. |
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MedDRA Classification |
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 |
To reveal the effect of 24-week therapy with n-3 FA (3 g EPA + DHA/day) both alone and in combination pioglitazon (15mg/day) in comparison to i) pioglitazon and placebo and ii) placebo alone in type 2 diabetic patients on • blood glucose control, insulin secretion and insulin resistance • lipid metabolism • variety of serum biomarkers of oxidative stress and inflammation • liver and muscle (musculus tibialis) fat content, body fat distribution • fat quantity in different departments (subcutaneous, visceral)
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E.2.2 | Secondary objectives of the trial |
I) To find novel markers of the beneficial effects on lipid metabolism and glycemic control, with a special focus on gene expression in adipose tissue and fatty acid pattern of serum and adipose tissue lipids II) To explore whether the effect of combination therapy on glucose and lipid metabolism is more beneficial than pioglitazon therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Type 2 diabetes mellitus as defined by the criteria of the American Diabetes Association and recognized by WHO, Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (American Diabetes Association, 2004) at least 3 months preceding screening
2. Concurrent T2DM therapy: Taking metformin as a monotherapy at stable dose in at least 2 months preceding week 0 procedures Previous chronic diabetes therapy will be limited to: sulfonylureas, glitinides, biguanides, glucosidase inhibitors such as acarbose, insulin.
3. HbA1c (IFCC): < 8 % (equals to aprox. 10% by DCCT), Triglycerides 2-6 mmol/l
4. Men and women who are 30 to 70 years of age
5. Body Mass Index between 25 and 45 (kg/m2)
6. Informed Consent: a signed and dated written consent obtained from the subject before any procedures are performed
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E.4 | Principal exclusion criteria |
1. Metabolic Disease including: Diagnosis of Type 1 diabetes mellitus Uncorrected thyroid dysfunction. (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 3 months prior to Screening, and who have a screening thyroid stimulating hormone (TSH) within the limits of normal may participate). 2. Significant weight gain or loss (as defined as > 5% of total body weight) within the past 3 months prior to Screening. 3. Regular use of insulin in previous 3 months 4. History of clinically significant cardiovascular disease including: Documented myocardial infarction in the past year Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery in the previous year and no subsequent angina Unstable angina Congestive heart failure (CHF) classified as New York Heart Association (NYHA) Class II, III or IV heart failure 5. Blood pressure > 150/100mmHg or HR > 100 beats/minute. Subjects using antihypertensives must be on stable doses during the 3 months prior to Screening and during the trial. 6. If a subject is receiving lipid-lowering therapy, then they must have been on the same dose of therapy for the past 3 months, concomitant fenofibrate therapy is not allowed and must be withdrawn at least 1 month ahead of week 0 procedures. 7. Is currently lactating, pregnant or actively trying to become pregnant. 8. Has a significant renal impairment as defined by serum creatinine > 150umol/L. 9. Has a documented history of chronic or advanced hepato-biliary disease including a history of, or positive laboratory results for hepatitis (hepatitis B surface antigen, hepatitis B core antigen, and hepatitis C antibody) at Screening. Has clinically significant hepatic enzyme elevation greater than 2.5 times the upper limit of the reference range value /alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) / Has a total bilirubin level that is > 1.5 times the ULRR at Screening. 10. Has a history of alcohol or substance abuse within the past year 11. Is currently taking and will not stop prohibited concomitant medications, see concomitant therapy. 12. Known allergy to any of the capsule excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician, contradicts participation. 13. Received treatment with an investigational drug or participated in any other clinical trial during the previous 3 months. 14. Clinically significant anemia (i.e., hemoglobin < 120.0g/L for males and < 110.0g/L for females) or any other abnormal hematological profile that is considered by the investigator to be clinically significant. 15. In the opinion of the Investigator has a risk of non-compliance with study procedures, or cannot read, understand, or complete study-related materials, particularly the informed consent. 16. Has any concurrent condition or any clinically significant abnormality identified on the screening physical examination, laboratory tests, electrocardiogram, including pulmonary, neurological or inflammatory diseases, which, in the opinion of the Investigator, may affect the interpretation of efficacy and safety data, or which otherwise, contraindicates participation in a clinical trial with the chemical entity.
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E.5 End points |
E.5.1 | Primary end point(s) |
Differences between treatment by n-3 FA versus placebo vs. pioglitazon and placebo vs pioglitazon and n-3 FA. Change from baseline in above variables (see objective)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Double blind vs. n-3 FA, open vs. Pioglitazone |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |