E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypercholesterolaemia. |
Hipercolesterolemia |
|
E.1.1.1 | Medical condition in easily understood language |
High blood cholesterol level. |
Nivel alto de colesterol en sangre |
|
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 | 10020603 |
E.1.2 | Term | Hypercholesterolaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition 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 |
To evaluate the long-term safety and tolerability of SAR236553(REGN727) in high cardiovascular risk patients with hypercholesterolemia not adequately controlled with their current lipid modifying therapy (LMT). |
Evaluar el perfil de seguridad y tolerabilidad a largo plazo de SAR236553 en pacientes con alto riesgo cardiovascular con hipercolesterolemia no controlada adecuadamente con su terapia modificadora de lípidos (TML). |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of SAR236553 (REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo. - To evaluate the efficacy of SAR236553 (REGN727) on LDL-C levels at other time points. |
- Evaluar el efecto de SAR236553 sobre los niveles de colesterol unido a lipoproteínas de baja densidad (C-LDL) tras 24 semanas de tratamiento en comparación con placebo. - Evaluar la eficacia de SAR236553 sobre los niveles de C-LDL en otros momentos de evaluación. |
|
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 |
1-Pharmacogenomics analysis - Date: 2011-11-29 - Version 1 - Related objectives: Identify genetic associations with clinical or biomarker response to PCSK9 inhibition, hyperlipidemia, or cardiovascular disease.
2- Opthamological Sub-study - Date: 2011-11-29 - Version 1 - Related objectives: to assess the clinical ophthalmic safety of SAR236553 in high cardiovascular risk patients with hypercholesterolemia not adequately controlled with their LMT. |
1. Análisis farmacogenómico, version 1 de fecha 29-11/2011. Objetivos: Se realizará un subestudio farmacogenómico opcional para identificar las asociaciones genéticas con la respuesta clínica o de los biomarcadores a la inhibición de PCSK9, la hiperlipidemia o la cardiopatía vascular. 2. Sub-estudio oftalmológico, version 1 de fecha 29-11/2011. Objetivos: Evaluar la seguridad oftálmica clínica de SAR236553 en pacientes con alto riesgo cardiovascular con hipercolesterolemia no controlada adecuadamente con su TML. |
|
E.3 | Principal inclusion criteria |
Either A or B below and not adequately controlled with a maximally tolerated stable daily dose of statin for at least 4 weeks prior to the screening visit with or without other lipid modifying therapy (LMT). A) Patients with heterozygous familial hypercholesterolemia (heFH) with or without established coronary heart disease (CHD) or CHD risk equivalents OR B) Patients with hypercholesterolemia together with established CHD or CHD risk equivalents. |
Cualquiera de las opciones A o B siguientes y no estar adecuadamente controlado con la dosis estable máxima tolerada de estatina* durante al menos 4 semanas antes de la visita de selección (semana -2) con o sin otra terapia modificadora de lípidos (TML). A) Pacientes con hipercolesterolemia familiar heterocigota (HFh) con o sin cardiopatía coronaria (CPC) confirmada o equivalentes de riesgo de CPC O B) Pacientes con hipercolesterolemia y CPC confirmada o equivalentes de riesgo de CPC. |
|
E.4 | Principal exclusion criteria |
? LDL-C <100 mg/dL (< 2.59 mmol/L) at the screening visit ? Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate for at least 6 weeks, as applicable, prior to the screening visit or from screening to randomization. ? Currently taking a statin that is not simvastatin, atorvastatin, or rosuvastatin taken daily at a registered dose. ? Fasting serum TG > 400 mg/dL (>4.52 mmol/L) at the screening visit |
? C-LDL <100 mg/dl (< 2,59 mmol/l) en la visita de selección (semana -2). ? Sin dosis estable de TML (incluidas estatinas) durante un mínimo de 4 semanas o fenofibrato durante un mínimo de 6 semanas, según proceda, antes de la visita de selección (semana -2) o desde la selección hasta la aleatorización. ? Administración actual de una estatina distinta de simvastatina, atorvastatina o rosuvastatina a diario en una dosis autorizada. ? Dosis diarias superiores a atorvastatina 80 mg, rosuvastatina 40 mg o simvastatina 40 mg (excepto en caso de pacientes que llevan más de un año tomando simvastatina 80 mg, que sí son elegibles). ? Valores séricos en ayunas de TG > 400 mg/dl (>4,52 mmol/l) en la visita de selección (semana - 2) ? Uso de fibratos distintos al fenofibrato durante las 6 semanas anteriores a la visita de selección (semana -2) o previsión de utilizarlos. ? C-LDL >160 mg/dl (4,14 mmol/l) en la visita de selección (semana -2) Y el paciente solo recibe monoterapia con estatinas sin TML adicional. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of safety parameters (adverse events [including adjudicated cardiovascular events, laboratory data, vital signs, and ECG] |
Parámetros de seguridad (acontecimientos adversos [incluidos acontecimientos cardiovasculares confirmados], datos analíticos, constantes vitales y ECG) evaluados durante el estudio. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 20 months |
Hasta los 20 meses |
|
E.5.2 | Secondary end point(s) |
Percent change in calculated low density lipoprotein cholesterol (LDL-C) |
El cambio porcentual registrado en los valores calculados de C-LDL entre el inicio y la semana 24 (como momento de evaluación principal de la eficacia). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 24 |
Desde el inicio hasta la semana 24 |
|
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 118 |
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 | No |
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 |
Argentina |
Belgium |
Bulgaria |
Canada |
Chile |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Guatemala |
Hungary |
Israel |
Italy |
Mexico |
Netherlands |
Norway |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
South Africa |
Spain |
Sweden |
Ukraine |
United Kingdom |
United States |
|
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
|
LVLS |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |