E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
high-risk hyperlipidaemia |
Hiperlipidemia de alto riesgo |
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E.1.1.1 | Medical condition in easily understood language |
Increased level of blood cholesterol |
Nivel elevado de colesterol en sangre |
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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 |
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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 | 10049593 |
E.1.2 | Term | Familial hypercholesterolaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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). |
El objetivo principal de este estudio es comparar la eficacia de pitavastatina 1 mg una vez al día, 2 mg una vez al día y 4 mg una vez al día con el placebo en términos del porcentaje de reducción del C-LDL en niños y adolescentes con hiperlipidemia de alto riesgo en fase estable (Semana 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. |
Los objetivos secundarios de este estudio son los siguientes: ? Comparar la eficacia de pitavastatina 1 mg una vez al día, 2 mg una vez al día y 4 mg una vez al día con el placebo en términos del cambio o el cambio porcentual de los parámetros secundarios de lípidos en niños y adolescentes con hiperlipidemia de alto riesgo durante doce semanas; ? Medir los parámetros de FC en cada concentración de dosis y ? Comparar la seguridad y la tolerabilidad de pitavastatina 1 mg una vez al día, 2 mg una vez al día y 4 mg una vez al día con el placebo en niños y adolescentes con hiperlipidemia de alto riesgo. |
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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. |
Los pacientes son aptos para el estudio si se cumplen todos los criterios siguientes: 1. Varones o mujeres de 6 años o más y de menos de 17 años en la randomización; 2. Presentar concentraciones de C-LDL en ayunas iguales o superiores a 160 mg/dl (4,1 mmol/l) o C-LDL igual o superior a 130 mg/dl (3,4 mmol/l) si se dan los siguientes factores de riesgo adicionales: ? Varones; ? Antecedentes familiares de cardiopatía prematura definida como infarto de miocardio antes de los 50 años en un pariente de segundo grado o antes de los 60 en un pariente de primer grado con al menos un pariente (padre, abuelo o hermano) afectado; ? Presencia de C-HDL bajo (inferior a 45 mg/dl) o TG alto (superior a 150 mg/dl); ? Presencia de lipoproteína(a) alta (superior a 75 nmol/l); ? Presencia de diabetes mellitus tipo 2 diagnosticada por el médico responsable de conformidad con las directrices actuales o ? Presencia de hipertensión definida como tensión arterial sistólica y diastólica por encima del percentil 95 para edad y talla; 3. Que no haya tomado medicamentos hipolipemiantes en las cinco semanas previas al screening o en las cuatro semanas previas a la visita de cumplimiento de los requisitos de lípidos en la Semana -1; 4. Haber guardado la dieta correspondiente durante al menos ocho semanas; 5. Las mujeres postmenárquicas no deben estar embarazadas o en lactancia y, si son sexualmente activas, deben utilizar un método anticonceptivo fiable y 6. Se debe obtener el consentimiento informado por escrito y el asentimiento (si es necesario) conforme se estipule en las normativas locales. |
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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. |
Se excluyen a los pacientes para el estudio si se cumple alguno de los criterios siguientes: 1. No es capaz o no quiere tomar el fármaco del estudio; 2. TG en ayunas superior a 400 mg/dl (4,5 mmol/l) 3. Hipercolesterolemia familiar homocigótica; 4. Otras causas secundarias de hiperlipidemia (por ej. hipotiroidismo, infección por el virus de la inmunodeficiencia humana, lupus eritematoso sistémico, transplante de órgano, neoplasia maligna previa, síndrome nefrótico, enfermedad por almacenamiento de glucógeno); 5. Antecedentes previos de intolerancia a las estatinas, efectos adversos con el empleo de otra estatina o hipersensibilidad a cualquier excipiente del fármaco del estudio; 6. Necesidad de fármacos hipolipemiantes que no sean estatinas; 7. Tratamiento mediante aféresis; 8. Uso de medicamentos concomitantes que puedan interferir con los objetivos del estudio; 9. Diabetes mellitus tipo 1; 10. Diabetes mellitus tipo 2 mal controlada definida como hemoglobina A1c >9,0% en el screening; 11. Insuficiencia renal grave definida como creatinina sérica superior a 2,0 mg/dl en el screening; 12. Hipertensión no controlada: 13. Enfermedad tiroidea sin tratar; 14. Insuficiencia hepática grave, hepatopatía activa o aumento constante de alanina aminotransferasa o aspartato aminotransferasa 3 veces superior del límite superior de la normalidad (LSN); 15. Miopatía activa o creatina cinasa tres veces superior al LSN (a menos que se explique por el ejercicio); 16. Valores en los análisis de screening dentro de los valores de referencia correspondientes siguientes según la edad/sexo evaluados por el laboratorio central: ? Hemoglobina inferior a 10g/dl para los hombres o inferior a 9 g/dl para las mujeres o ? Fosfatasa alcalina dos veces superior al LSN para la edad; 17. Cualquier otra alteración en los análisis que podría comprometer la seguridad del paciente debido a su participación en el estudio; 18. Neoplasia maligna en los cinco años previos; 19. Fumador actual o antecedentes de drogadicción o alcoholismo; 20. Hospitalización por cualquier motivo en los treinta días previos a la administración del fármaco del estudio; 21. Antecedentes de cirugía mayor en los tres meses previos al screening; 22. Una dolencia que, en opinión del Investigador, podría hacer peligrar la evaluación de la seguridad y/o constituir un riesgo significativo para la seguridad del paciente o 23. Participación en otro estudio clínico en el que haya un fármaco en fase de investigación clínica durante el transcurso de este estudio o en los treinta días previos a la firma del documento de consentimiento informado/asentimiento de este estudio. |
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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. |
El criterio de valoración principal de la eficacia es el cambio porcentual en C-LDL desde el valor inicial al criterio de valoración de la Semana 12 para el grupo completo de análisis. |
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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. |
? Cambio porcentual en C-LDL con respecto al valor inicial durante las doce semanas de tratamiento (Semana 4, Semana 8 y Semana 12); ? Porcentajes de pacientes que alcanzan los objetivos mínimo (130 mg/dl [3,4 mmol/l]) e ideal (110 mg/dl [2,8 mmol/l]) de la Asociación Estadounidense del Corazón (AHA ? American Heart Association) durante las doce semanas de tratamiento; ? Cambios porcentuales en el colesterol de lipoproteínas de alta densidad (C-HDL), colesterol de lipoproteínas de no alta densidad (C-no-HDL), colesterol total (CT), TG, apoliproteína A1( Apo A1) y apolipoproteína B (Apo B) desde el momento inicial durante las doce semanas de tratamiento y ? Cambios en la proporción CT:C-HDL, proporción C-no-HDL:C-HDL y proporción ApoB:Apo A1 desde el momento inicial durante las doce semanas de tratamiento. |
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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
| 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 | 2 |
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 | 0 |
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 years | 0 |
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 |