E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetic patients, as defined by the WHO without CVD and with CVD (Cardiovascular disease), with combined hyperlipidemia. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027763 |
E.1.2 | Term | Mixed hyperlipidemia |
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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 |
- To demonstrate the superiority of the efficacy of Fenofibrate 160mg/Pravastatin 40mg combination versus Simvastatin 20 mg, in type 2 diabetic patients without CVD and with combined hyperlipidemia and to describe the safety of the combination. - To demonstrate the superiority of the efficacy of Fenofibrate 160mg/Pravastatin 40mg combination + Ezetimibe 10 mg versus Simvastatin 20 mg + Ezetimibe 10 mg, in type 2 diabetic patients with CVD and with combined hyperlipidemia and to describe the safety of Fenofibrate 160mg/Pravastatin 40mg combination + Ezetimibe 10 mg.
These two objectives will be demonstrated by an evaluation of the mean percent changes in plasma non-HDL cholesterol levels at the end of the efficacy period compared to baseline. |
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E.2.2 | Secondary objectives of the trial |
· To evaluate the percentage of patients who achieve the therapeutic goals with regards to non-HDL cholesterol and LDL-C levels at the end of the efficacy period, as defined in the NCEP ATP III · To assess and compare the evolution of the following lipid parameters: LDL-C, HDL-C, TG, total cholesterol at the end of the efficacy period · To assess and compare the evolution of ApoA1 and ApoB levels, and of the ratio ApoB/ApoA1 at the end of the efficacy period · To evaluate the changes in CRP values, fibrinogen values and homocystein values at the end of the efficacy period · To compare the safety profiles of Simvastatin 20 mg and Fenofibrate 160 mg/Pravastatin 40 mg combination with and without Ezetimibe during the 12-week efficacy period, and to describe the safety profile of Fenofibrate 160 mg/Pravastatin 40mg combination with and without Ezetimibe 10 mg during the 12-week safety period.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Selection criteria : · Male or female, aged 18 years and older · Type 2 diabetic patients as defined by the WHO without CVD and with CVD · Patients presenting a known combined hyperlipidemia (to be documented by physician) · Patients following a standardized diet for at least three months before the selection visit and to be maintained stable throughout the study · Able to comply with all study procedures · Provide written, informed consent to participate in the study, indicated by a personal signature and date on the patient consent form · If the patient is female and of childbearing potential, she must be using an efficient mean of birth control, as determined by the investigator and provide a negative serum pregnancy test
Inclusion criteria : · Patients with non-HDL-C > or = 130 mg/dl (3.36 mmol/l) [or LDL C > or =100 mg/dl (2.6 mmol/l)] and without CVD, or non-HDL-C > or =100 mg/dl (2.59 mmol/l) [or LDL-C> or = 70 mg/dl (1.8 mmol/l)] and with CVD, at the laboratory sample taken one week before the randomisation visit · TG > or =150 mg/dl (1.7 mmol/l) and < or =600 mg/dl (6.8 mmol/l) at the laboratory sample taken one week before the randomisation visit · Patients always respecting the selection criteria |
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E.4 | Principal exclusion criteria |
· Secondary or iatrogenic dyslipidemia · Hyperlipidemia type I-IIa-IV-V · Abnormal liver function [hepatocellular insufficiency, chronic or active liver disease, biliary tract disease, sustained elevation of serum liver enzymes (simultaneous ASAT/SGOT and ALAT/SGPT > 2x ULN at laboratory sample B1 or B2)] · CPK > 3x ULN at laboratory sample B1 or B2 · Abnormal renal function (clearance of creatinine < 60 ml/mn and creatinemia > 15 mg/l at laboratory sample B1 or B2) or any renal disease likely to lead to renal dysfunctions · Patients who had an acute cardiovascular episode within the 3 months previous to the start of the trial, or with a history of coronary angioplasty with mounting of a Stent within the past 6 months · Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg) under blood pressure treatment· Evidence of any other unstable or untreated clinically significant immunological, neoplastic, endocrine, haematological, gastrointestinal, neurological or psychiatric abnormalities or medical disease · Presence of any other condition or illness, which, in the opinion of the investigator would interfere with optimal participation in the study and likely to jeopardize the planned termination of the study · Patients with any sensitivity or allergy to any of the products used within this clinical trial: known hypersensitivity to HMG-COA reductase inhibitors, fibric acid derivatives or ezetimibe · Uncontrolled primary hypothyroidism · Uncontrolled diabetes with HbA1c > 8.5% at laboratory sample B1 or B2 · Diabetes requiring insulin · Use of any of the prohibited medication as detailed in the non-permitted medication section · Non adherence to a stable standardized diet during the study · Patients with high alcohol consumption (above 21 beverages per week or with a recent history of alcoholism : one alcoholic beverage is defined as 30 mL distilled spirits, 120 mL wine, or 330 mL beer) · Patients with a personal or family history of hereditary muscle disease · Patients with poor cognitive function · Participation in any other clinical trial within 3 months before the selection visit · Childbearing potential woman not using an appropriate contraceptive method, pregnant or breastfeeding woman · Patient not covered by Health Insurance System and / or not in compliance with the recommendations of National Law in force · Participation in any other trials with the fenofibrate-pravastatin 160-40 mg SMB product · Compliance <80% during the run-in phase
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy endpoints : · Mean percent change in plasma non-HDL cholesterol levels at the end of the efficacy period compared to the baseline
Secondary Efficacy endpoints : · Percentage of patients who achieve the therapeutic goals concerning the non-HDL-C and LDL-C levels at the end of the efficacy period, as defined in the NCEP ATP III · Mean percent change of the following lipidemic parameters levels: LDL-C, HDL-C, TG, total cholesterol at the end of the efficacy period · Mean percent change of Apo A1, Apo B levels at the end of the efficacy period · Mean percent change of Apo B/Apo A1 ratio at the end of the efficacy period · Mean percent change of C Reactive Protein (CRP) values at the end of the efficacy period · Mean percent change of Fibrinogen values at the end of the efficacy period · Mean percent change of Homocysteine values at the end of the efficacy period
Safety profile will be compared and described using: Adverse events, Vital signs, Physical examination, Laboratory evaluation, Appearance of myopathy and/or rhabdomyolysis, Increase of transaminase levels, Increase of CPK, Increase of creatinemia and decrease of creatinine clearance, Withdrawals or drop-out rate. |
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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) | 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 |
The 6-week period prior to the inclusion and the safety period will be performed in open conditions |
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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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |