E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
high-risk hyperlipidaemia |
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E.1.1.1 | Medical condition in easily understood language |
Increased level of blood cholesterol |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062060 |
E.1.2 | Term | Hyperlipidaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020603 |
E.1.2 | Term | Hypercholesterolaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016205 |
E.1.2 | Term | Familial hyperlipidaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057099 |
E.1.2 | Term | Heterozygous familial hypercholesterolaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049593 |
E.1.2 | Term | Familial hypercholesterolaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
The primary objective of this study is to compare the efficacy of pitavastatin 1 mg QD, 2 mg QD, and 4 mg QD to placebo in terms of the percentage reduction in LDL-C in children or adolescent patients with high-risk hyperlipidaemia at steady state (Week 12). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are the following:
• To compare the efficacy of pitavastatin 1 mg QD, 2 mg QD, and 4 mg QD to placebo in terms of the change or percent change in secondary lipid parameters in children and adolescent patients with high-risk hyperlipidaemia over 12 weeks;
• To measure PK parameters at each dose level; and
• To compare the safety and tolerability of pitavastatin 1 mg QD, 2 mg QD, and 4 mg QD to placebo in children and adolescent patients with high-risk hyperlipidaemia over 12 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female ≥6 years of age and <17 years of age at randomisation;
2. Have fasting LDL-C levels ≥160 mg/dL (4.1 mmol/L) or LDL-C ≥130 mg/dL (3.4 mmol/L) if any of the following additional risk factors are present:
• Male;
• A family history of premature cardiovascular disease defined as a myocardial infarction before age 50 in a second-degree relative or before age 60 in a first-degree relative with at least 1 relative (parent, grandparent, or sibling) affected;
• Presence of low HDL-C (<45 mg/dL) or high TG (>150 mg/dL);
• Presence of high lipoprotein(a) (>75 nmol/L);
09 December 2011 vii12
• Presence of type 2 diabetes mellitus diagnosed by treating physician according to current guidances; or
• Presence of hypertension defined as systolic and diastolic blood pressures above the 95th percentile for age and size;
3. Have not taken any lipid-lowering medications in the 5 weeks prior to screening or in the 4 weeks prior to the lipid qualifying visit at Week -1;
4. Have been adherent to an appropriate diet for at least 8 weeks;
5. Females who are post-menarche must not be pregnant or breast feeding and, if sexually active, must be using a reliable form of contraception; and
6. Written informed consent and assent (if necessary) obtained as required per local regulations. |
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E.4 | Principal exclusion criteria |
1. Unable or unwilling to take study drug;
2. Fasting TG >400 mg/dL (4.5 mmol/L);
3. Homozygous familial hypercholesterolaemia;
4. Other secondary causes of hyperlipidaemia (eg, hypothyroidism, human immunodeficiency virus infection, systemic lupus erythematosus, organ transplantation, previous malignancy, nephrotic syndrome, glycogen storage disease);
5. Previous history of statin intolerance, adverse effects with other statin use, or hypersensitivity to any components of the study drug;
6. Need for non-statin lipid-lowering medications;
7. Apheresis therapy;
8. Use of any concomitant medication which may interfere with the objectives of the study;
9. Type 1 diabetes mellitus;
10. Poorly controlled type 2 diabetes mellitus defined as haemoglobin A1c >9.0% at screening;
11. Severe renal impairment defined as serum creatinine >2.0 mg/dL at screening;
12. Uncontrolled hypertension;
13. Untreated thyroid disease;
14. Severe hepatic impairment, active liver disease, or persistent elevation of alanine transaminase or aspartate transaminase >3 × the upper limit of normal (ULN);
15. Active muscle disease or creatine kinase >3 × ULN (unless explained by exercise);
16. Screening laboratory values within the following age/gender appropriate reference ranges as assessed by the central laboratory:
• Haemoglobin <10 g/dL for males or <9 g/dL for females or
• Alkaline phosphatase >2 × ULN for age;
17. Any other laboratory abnormality that could compromise patient safety because of study participation;
18. Malignancy during the past 5 years;
19. Current smoker or history of drug or alcohol abuse;
20. Hospitalisation for any cause within 30 days prior to the administration of study drug;
21. History of major surgery in the 3 months prior to screening;
22. Any medical condition which, in the judgment of the Investigator, would jeopardize the evaluation of safety and/or constitute a significant safety risk to the patient; or
23. Participation in another clinical study involving an investigational drug during the course of this study or within 30 days prior to signing the informed consent/assent form for this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this study is the percent change in LDL-C from baseline to Week 12 endpoint. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Percent change in LDL-C from baseline over 12 weeks of treatment (Week 4, Week 8, and Week 12);
• Percentages of patients who achieve AHA minimal (130 mg/dL [3.4 mmol/L]) and ideal (110 mg/dL [2.8 mmol/L]) LDL-C targets over 12 weeks of treatment;
• Percent changes in HDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), TC, TG, apolipoprotein A1 (Apo A1), and Apo B from baseline over 12 weeks of treatment; and
• Changes in TC:HDL-C ratio, non-HDL-C:HDL-C ratio, and Apo B:Apo A1 ratio from baseline over 12 weeks of treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 26 |