| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with type 2 diabetes mellitus and dyslipidemia |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
|
| 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 demonstrate that, under conditions of first-line drug treatment in antidiabetic drug naïve/drug free patients (no antidiabetic drug treatment in the last 6 months), with T2DM and dyslipidemia, after 24 weeks treatment:
• The efficacy of fenofibrate and metformin FC on glycemic control (HbA1c) is not inferior to that of rosiglitazone,
• The efficacy of fenofibrate and metformin FC on triglyceride control is superior to that of rosiglitazone |
|
| E.2.2 | Secondary objectives of the trial |
To assess the efficacy of fenofibrate and metformin FC compared to rosiglitazone on the HbA1c, TG at 12 weeks.
To assess the efficacy of fenofibrate and metformin FC compared to rosiglitazone on the HbA1c, TG separately, in the following subgroups of interest:
• TG level at baseline: 150 mg/dL ≤ TG < 300 mg/dL (1.69 mmol/L ≤ TG < 3.38 mmol/L) and 300 mg/dL ≤ TG ≤ 400 mg/dL (3.38 mmol/L ≤ TG ≤ 4.52 mmol/L),
• Male / female,
• HbA1c level at baseline: 6.5% ≤ HbA1c ≤ 8% and 8% < HbA1c ≤ 9.5%,
• Concomitant use of statin.
To assess the efficacy of fenofibrate and metformin FC compared to rosiglitazone on the following parameters:
• FPG,
• TC,
• HDL-C,
• LDL-C,
• LDL particle size,
• Non HDL-C,
• Apo AI,
• Apo B,
• Apo CIII,
• Body weight.
To assess the safety of fenofibrate and metformin FC and rosiglitazone based on different parameters. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
At inclusion (V0):
1. Male or female aged from 18 to 75 years old,
2. With type 2 diabetes mellitus and dyslipidemia inadequately controlled with lifestyle modifications (diet and exercise),
3. With antidiabetic drug status as follows:
• Antidiabetic drug naive patients: who have never been on prior antidiabetic drug treatment,
or,
• Antidiabetic drug free patients: who have not received antidiabetic drug treatment in the last 6 months,
4. Having signed a written informed consent.
At randomization (V1):
5. FPG ≥ 126 mg/dL dL (≥ 7.0 mmol/L) and < 300 mg/dL (< 16.7 mmol/L). Glycemic status of the patients will be confirmed based on two FPG assays, BV0 and BV1,
6. HbA1c ≥ 6.5% and ≤ 9.5%,
7. Hypertriglyceridemia with or without hypercholesterolemia, defined by TG ≥ 150 mg/dL and ≤ 400 mg/dL (TG ≥ 1.69 mmol/L and ≤ 4.52 mmol/L), assayed at BV1. |
|
| E.4 | Principal exclusion criteria |
Patient with any of the following conditions will not be included in the trial:
1. Known Type 1 diabetes,
2. With LDL-C > 130mg/dL (3.35 mmol/L),
3. In cardiovascular secondary prevention,
4. Body mass index > 40 kg/m2,
5. Women who are not postmenopausal if they are not surgically sterilized (i.e. bilateral tubal ligation, bilateral or two unilateral oophorectomies, hysterectomy), or not using adequate contraceptive precautions,
6. Pregnant or lactating women,
7. Known hypersensitivity to fibrates, metformin, rosiglitazone or any of their components or known photoallergic or phototoxic reactions under treatment with fibrates or ketoprofen,
8. Known allergy to peanut or arachis oil or soya lecithin or related products due to the risk of hypersensitivity reactions,
9. Having received an investigational drug in the last 30 days before date of inclusion,
10. Unable or unwilling to comply with the protocol and the standard diet and exercise recommendations,
11. Likely to withdraw from the study before its completion.
Concomitant medications:
12. Treated within the last 6 months before randomization with any antidiabetic drug treatment,
13. Treated within the last 2 months before randomization with a lipid-lowering drug (except statins). Patients who were on a statin before inclusion may be included provided the dose does not exceed the maximum daily dose authorized in the study ) and is kept constant throughout the study.
14. Treated within the last 2 months before randomization with oral anticoagulants, with cyclosporin A, and any other immunosuppressive agent, with protease inhibitors (indinavir, ritonavir, saquinavir, …), for obesity by medical treatment (orlistat, sibutramine…) and/or surgery (gastroplasty, bypass,…), with rifampin (inducer of CYP2C8)
15. Change within the last 2 months before randomization, and during the course of the study, in the medications that could interfere with the lipid or glycemic profile.
Associated diseases or conditions:
16. Diabetic ketoacidosis, diabetic pre-coma,
17. Current chronic pancreatitis, or identified risk or known history of acute pancreatitis,
18. Known cholelithiasis without cholecystectomy,
19. Significant hepatic disease: AST and/or ALT > 2 times the upper limit of normal (ULN),
20. Musculoskeletal disease with increased creatine phosphokinase (CPK) > 3 times ULN,
21. Renal failure or renal dysfunction defined by a creatinine clearance < 60 mL/min as calculated with the Cockroft-Gault algorithm: creatinine clearance = [(140 - age) x weight (kg) / 7.2 x serum creatinine (mg/L)] for males and [x 0.85] in females,
22. Acute conditions with the potential to alter renal function (such as dehydration, severe infection, shock, intravascular administration of iodinated contrast agents),
23. Acute or chronic disease which may cause tissue hypoxia such as respiratory failure,
24. Known congestive heart failure or past medical history of congestive heart failure (class I to IV),
25. Known abnormal thyroid hormone levels, or high thyroid stimulating hormone (TSH) level. (clinically euthyroid subjects on stable replacement doses of thyroid hormone are eligible for inclusion),
26. Other uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins,
27. Patients particularly susceptible to hypoglycemic effects, such as debilitated, or malnourished patients, acute alcohol intoxication, excessive alcohol intake,
28. Known gastric or peptic ulcer or intestinal disease within the previous 3 months of randomization capable of modifying the intestinal absorption of the drugs,
29. Any other severe pathology such as cancer or mental illness or degenerative disease that would limit study evaluation or participation.
30. Known diabetic retinopathy, macular edema, or symptoms suggestive of macular edema including blurred or distorted vision, decreased color sensitivity, decrease dark adaptation.
In addition in patients aged under 35 years the following exclusion criteria will apply:
31. Body mass index < 25 kg/m2,
32. Ever been treated by Insulin,
33. Family history of type 1 diabetes.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints :
The primary analysis on the full analysis set (FAS) will consist in testing both non-inferiority on HbA1c and superiority on TG using an analysis of covariance (ANCOVA) (if no violation of the usual assumptions).
The study will be considered as positive if non-inferiority on HbA1c and superiority on TG are demonstrated in the FAS.
Secondary Efficacy Endpoints:
The main analysis will be repeated at 12 weeks as secondary analysis.
The secondary parameters (lipids parameters, glucose, weight) will be analyzed using an analysis of covariance (ANCOVA) to compare the two treatments.
|
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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) | Yes |
| 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 | No |
| 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 |
| 2 treatments administered through forced titration over 2 periods of 12 weeks each |
|
| 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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