E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Hypercholesterolemia (Heterozygous Familial) Primary Hypercholesterolemia (Non-familial) |
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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 | 10020604 |
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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 | 10057079 |
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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 determine the effect of ezetimibe 10 mg/day compared to placebo on the reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 12 weeks of treatment in children ≥ 6 to ≤10 years old with primary hypercholesterolemia (Heterozygous Familial Hypercholesterolemia [HeFH] and nonfamilial). |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of ezetimibe 10 mg/day compared to placebo on total cholesterol (TC), apolipoprotein B (Apo B), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglycerides (TG) from baseline to 12 weeks of treatment. |
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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 |
FARMACOCINETICA/FARMACODINAMICA: Versione:Am 1 Data:2010/07/30 Titolo:Studio randomizzato, in doppio cieco, per gruppi paralleli, controllato verso placebo per la valutazione della sicurezza ed efficacia di Ezetimibe in monoterapia in bambini (di eta` compresa fra 6 e 10 anni) con ipercolesterolemia primaria (eterozigote familiare e non familiare) Obiettivi:Criteri di Valutazione per il Sottostudio di Farmacocinetica (PK): nel sotto-studio di Farmacocinetica alla Visita 5 saranno raccolti dei campioni ematici in almeno 12 soggetti. Il sottostudio PK fornira` un’analisi descrittiva del profilo farmacocinetico di ezetimibe 10 mg/die. Per ezetimibe e per ezetimibe totale saranno determinati Cmax, AUC(0-12hr), AUC(0-24hr) e Tmax e saranno fornite analisi descrittive.
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E.3 | Principal inclusion criteria |
The subject must fulfill ALL the criteria listed below for entry. 1. Each subject may be of either sex and of any race/ethnicity, and must be ≥6 and ≤10 years of age, with a diagnosis of primary hypercholesterolemia(heterozygous familial or nonfamilial) despite being on a lipid-lowering diet for at least 3 months. 2. Any subject meeting at least one of the following clinical criteria items, ``a-e`` below,will be considered to have heterozygous familial hypercholesterolemia: a. genotype-confirmed HeFH with written documentation of the genetic diagnosis prior to or at the time of screening and LDL-C >159 mg/dL (4.12 mmol/L) and <400 mg/dL (10.36 mmol/L). b. LDL-C >159 mg/dL (4.12 mmol/L) and <400 mg/dL (10.36 mmol/L) with at least one biological parent with genotype-confirmed HeFH and a historical untreated LDL-C of >159 mg/dL. c. LDL-C >159 mg/dL (4.12 mmol/L) and <400 mg/dL (10.36 mmol/L) with at least one biological parent with an untreated LDL-C value of at least 210 mg/dL (5.44 mmol/L) not associated with a disorder known to produce secondary elevation of LDL-C d. LDL-C >159 mg/dL (4.12 mmol/L) and <400 mg/dL (10.36 mmol/L) with tendinous xanthomas, not associated with a disorder known to produce secondary elevation of LDL-C. e. LDL-C >189 mg/dL (4.90 mmol/L) and <400 mg/dL (10.36 mmol/L) and a family history of hypercholesterolemia 3. Each subject with nonfamilial primary hypercholesterolemia must have a LDL-C of >159 mg/dL (4.12 mmol/L) and <400 mg/dL (10.36 mmol/L) at Visit 3. 4. Each subject must have been on a diet in accordance with the American Heart Association/American Academy of Pediatric guidelines. 5. Each subject’s complete blood count [CBC], blood chemistry, urinalysis, and steroid hormone levels must be within normal limits or clinically acceptable to the investigator. 6. Each subject must be free of any clinically significant disease, other than hypercholesterolemia, that would interfere with the study evaluations. 7. Each subject must be willing to participate in the study and to complete all study related procedures. 8. Each subject’s parent/guardian must be willing to give written informed consent on his/her behalf. 9. Each subject must be able to adhere to dosing requirements and visit schedules. 10.All females of child-bearing potential must have a negative serum pregnancy test(beta-human chorionic gonadotropin [hCG]) at screening. |
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E.4 | Principal exclusion criteria |
Each subject must not: 1. have known hypersensitivity or any contraindication to ezetimibe. 2. have a height below the 3rd percentile for age and sex (using accepted standards). 3. be in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study. 4. have an underlying disease likely to limit life span to less than 1 year. 5. have use of any investigational drugs within 30 days of study entry. 6. have participation in any other clinical study, unless permission is given by this sponsor. 7. be a member or a family member of the personnel of the investigational or sponsor staff directly involved with this trial. 8. be a female of child-bearing potential who is pregnant, intends to become pregnant, or is nursing 9. be a female of child-bearing potential who will not abstain from sex or use a medically acceptable method of birth control in the opinion of the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is percent change from baseline in LDL-C at Week 12. The key secondary efficacy endpoint for the current trial is percent change from baseline to 12 weeks in the ezetimibe group compared univariately with the changes in the same respective variables in the placebo group for the following variables: a. TC; b. non-HDL-C; c. TG; d. Apo B; e. HDL-C. |
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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 | 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 | No |
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) | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | 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
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |