E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
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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 assess the effect of AVE5530 on LDL-C levels over a period of 4 weeks in patients with mild to moderate hypercholesterolemia. |
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E.2.2 | Secondary objectives of the trial |
-To assess the effects of AVE5530 on other lipid plasma levels (e.g. Total cholesterol, HDL-C, triglycerides, Apolipoprotein AI, AII and Apolipoprotein B) over a period of 4 weeks -To assess the effects of administration of AVE5530 25 mg at dinner on LDL-C and other lipid levels over a period of 4 weeks -To assess the safety and tolerability of AVE5530 over a period of 4 weeks |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
see section of the protocol: 9.3 Pharmacokinetics 9.3.1 Sampling time "The blood samples will be performed in a subset of the subjects" |
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E.3 | Principal inclusion criteria |
-Male aged ≥ 18 years or postmenopausal women at screening -With mild to moderate primary hypercholesterolemia: LDL-C ≥ 130mg/dL and ≤ 250 mg/dL (≥3.36 mmol/L and ≤ 6.46 mmol/L) under controlled-diet at Week-1 (Day-7) and stabilized at the end of lead-in period (the difference between two consecutive LDL-C values obtained during the lead-in period should not exceed 12% see section 9.1.1.1)
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E.4 | Principal exclusion criteria |
• Exclusion criteria related to study methodology (and stage of clinical development of the sanofi-aventis compound): − Refusal or inability to give informed consent to participate in the study − Inability to follow verbal and written instructions − Administration of other investigational drugs within 30 days prior to screening visit (Visit 1) − Patient considered by the Investigator as unsuitable candidates to receive an investigational drug − Presence of any other conditions (e.g. geographic, social….) actual or anticipated, that the Investigator feels would restrict or limit the patient’s participation for the duration of the study − Patient who is a member of the site staff directly involved in the study (including the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator or other) or a close relative thereof
• Exclusion criteria related to endocrine/metabolic or other disorders: − Presence of any clinically significant endocrine disease known to influence serum lipids or lipoproteins. Note: euthyroid patients on replacement therapy can be included if the dosage of thyroxine is stable for at least 3 months prior to screening. − Patients with type 1 diabetes − Presence or history of cancer within the past five years with the exception of adequately treated localized basal skin cancer or in situ uterine cervical cancer − Patients with a history (during the past six months) or concurrent DSM-IV substance abuse or dependence (excluding nicotine and caffeine) − Presence of any severe medical or psychological conditions that in the opinion of the Investigator would compromise the patient’s safety or successful participation in the study or might interfere with evaluation of study medication
• Exclusion criteria related to laboratory and or ECG findings: − Positive test for hepatitis B surface antigen and/or hepatitis C antibody − TG ≥ 300 mg/dL (3.39 mmol/L) − Abnormal sensitive TSH level (> ULN or < LLN) according to the normal values of the Central Laboratory − Neutrophils < 1,500 /mm3 − Fasting plasma glucose > 160 mg/dL (8.9 mmol/L) − Impaired renal function, as shown but not limited to serum creatinine > 150 µmol/L − Active liver disease, as shown but not limited to alanine aminotransferase (ALT) or aspartate amino-transferase (AST) > 2xULN − Presence of any clinically significant abnormality on the ECG performed at the screening visit (such as but not limited to QTc ≥ 500 ms)
• Exclusion criteria related to previous or concomitant medications: − Within one month prior to screening visit and/or at the time or after the screening visit, administration of any lipid lowering treatment
• Exclusion criteria related to the active calibrator, ezetimibe: − As per SPC (Appendix A) Pregnant or breast-feeding women, History of hypersensitivity to any of components of ezetimibe − In addition, CPK > 2xULN, since some rare cases of myopathy and rhabdomyolysis have been reported in post-marketing experience of ezetimibe. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change in LDL-C from baseline to 4 weeks |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 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 | No |
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
| 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 | 5 |
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 | 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 |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |