E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypercholesterolemia |
Ipercolesterolemia |
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E.1.1.1 | Medical condition in easily understood language |
Hypercholesterolemia |
Ipercolesterolemia |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
E.1.2 | System Organ Class | 100000004861 |
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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 demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in patients with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy. To evaluate the safety and tolerability of alirocumab in patients with diabetes treated with insulin. |
¿ Dimostrare la superiorit¿ di alirocumab, in confronto al placebo, nella riduzione del valore calcolato delle lipoproteine a bassa densit¿ del colesterolo (LDL-C), in pazienti diabetici, in terapia con insulina e ad alto rischio cardiovascolare, non adeguatamente controllati con la massima dose tollerata di terapia ipolipemizzante ¿ Valutare la sicurezza e la tollerabilit¿ di alirocumab in pazienti diabetici in terapia con insulina
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E.2.2 | Secondary objectives of the trial |
To demonstrate that alirocumab is superior in comparison to placebo in its effects on other lipid parameters (ie, measured LDL-C, non-high-density lipoprotein cholesterol [non-HDL-C], apolipoprotein B [Apo B], total cholesterol [TC], lipoprotein a [Lp(a)]), high density lipoprotein cholesterol (HDL-C), triglyceride (TG) levels, triglyceride rich lipoproteins (TGRL), apolipoprotein A-1 (Apo A-1), apolipoprotein CIII (Apo C-III), and LDL particle number and size) |
¿ Dimostrare la superiorit¿ di alirocumab in confronto al placebo in termini di effetto su altri parametri lipidici (ossia LDL-C misurato, lipoproteine non ad alta densit¿ del colesterolo [non-HDL-C], apolipoproteina B [Apo B], colesterolo totale [TC], lipoproteina a [Lp(a)]), lipoproteine ad alta densit¿ (HDL-C), livelli di trigliceridi (TG), lipoproteine ricche di trigliceridi (TGRL), apolipoproteina A-1 (Apo A-1), apolipoproteina C-III (Apo C-III) e numero e dimensione delle particelle LDL). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with type 1 or type 2 diabetes treated with insulin whose LDL-C levels are not adequately controlled with maximally tolerated lipid-modifying therapy. LDL-C of 70 mg/dL or greater. 18 years of age or more. Glycosylated hemoglobin (HbA1c) less than 10%. History of cardiovascular disease (including CHD and/or CHD risk equivalents) and/or at least one additional cardiovascular risk factor. |
1) Pazienti con diabete di tipo 1 o 2 in terapia con insulina e con livelli di LDL-C non adeguatamente controllati dalla massima dose di statine tollerata dal paziente; 2) LDL-C pari a 70 mg/dl o maggiore; 3) Pazienti di età =18 anni; 4) Emoglobina glicosilata (HbA1c) <10% 5) Pazienti con anamnesi documentata di malattia cardiovascolare (CVD) (inclusa cardiopatia coronarica (CHD) e/o fattori di rischio equivalenti a CHD) e/o almeno un fattore di rischio cardiovascolare aggiuntivo. |
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E.4 | Principal exclusion criteria |
Not on a stable dose of statin or other lipid modifying therapy for at least 4 weeks prior to screening. Triglycerides >400 mg/dL. Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m^2 according to modification in diet of renal disease (MDRD) equation. Currently receiving or plans to receive renal replacement therapy (for example, hemodialysis). Change in weight of more than 5 kilograms within the prior 2 months. Not on a stable dose/regimen of insulin or other antidiabetic drugs for the past 3 months or plans to intensify insulin regimen during the study. Not treated with insulin for at least 6 months. Plans to start new lipid modifying therapy or change dose of current lipid modifying therapy during the study. Body mass index (BMI) >45 kg/m^2 or plans to undergo bariatric surgery, weight loss program, or initiate weight loss drugs during the study. History of recent decompensation of diabetes within the prior 2 months (for example, diabetic ketoacidosis). |
1) Pazienti in trattamento con una dose non stabile di LMT (incluse statine o altra LMT) per almeno 4 settimane prima della visita di screening; 2) Trigliceridi >400 mg/dl; 3) eGFR<15 ml/min/1,73 m2 in base all'equazione MDRD; 4) Attuale trattamento o previsione di terapia sostitutiva della funzionalità renale (ad es. emodialisi); 5) Peso instabile, definito come variazione di peso superiore a 5 kg nei 2 mesi precedenti la visita di screening; 6) Dose di insulina non stabile per almeno 3 mesi prima dello screening o probabile necessità di intensificazione del regime insulinico/anti-iperglicemico durante lo studio; 7) Pazienti non trattati con insulina per almeno 6 mesi; 8) Indice di massa corporea (BMI) >45 kg/m2 o previsione di chirurgia bariatrica, programma di dimagramento o di inizio di trattamento farmacologico per il dimagramento nel corso dello studio; 9) Anamnesi di recente scompenso del diabete nei 2 mesi precedenti la visita di screening (ad esempio, chetoacidosi diabetica); 10) Inizio pianificato di nuova LMT nel corso dello studio o di variazione di dosaggio della LMT attuale |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Percent change in calculated LDL-C in the intent to treat (ITT) population 2) Number of patients with adverse events |
1)Variazione percentuale del livello calcolato di LDL-C nella popolazione intent-to-treat (ITT) 2) Numero di pazienti con eventi avversi
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1- From baseline to Week 24 2- From baseline to Week 32
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1) Dal basale alla settimana 24 2) Dal basale alla settimana 32
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E.5.2 | Secondary end point(s) |
1. Percent change in calculated LDL-C in the modified ITT (mITT) population 2. Percent change in measured LDL-C in the ITT population 3. Percent change in calculated LDL-C in the ITT population 4. Percent change in non-HDL-C in the ITT population 5. Percent change in Apo B in the ITT population 6. Percent change in total cholesterol in the ITT population 7. Proportion of patients reaching calculated LDL-C < 70 mg/dL in the mITT population Proportion of patients reaching calculated LDL-C < 50 mg/dL in the mITT population 8. Proportion of patients reaching non-HDL < 100 mg/dL in the mITT population Proportion of patients reaching non-HDL < 80 mg/dL in the mITT population 9. Percent change in Lp(a) in the ITT population Percent change in HDL-C in the ITT population 10. Percent change in TG in the ITT population Percent change in LDL-C particle number in the ITT population Percent change in LDL-C particle size in the ITT population
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1. Variazione percentuale del livello calcolato di LDL-C nella popolazione modificata intent-to-treat (mITT) 2. Variazione percentuale del livello misurato di LDL-C nella popolazione intent-to-treat (ITT) 3. Variazione percentuale del livello calcolato di LDL-C nella popolazione intent-to-treat (ITT) 4. Variazione percentuale del livello di non HDL-C nella popolazione intent-to-treat (ITT) 5. Variazione percentuale del livello di Apo B nella popolazione intent-to-treat (ITT) 6. Variazione percentuale del livello di colesterolo totale nella popolazione intent-to-treat (ITT) 7. Proporzione di pazienti che raggiungono un livello calcolato di LDL-C <70 mg/dl nella popolazione modificata intent-to-treat (mITT) Proporzione di pazienti che raggiungono un livello calcolato di LDL-C <50 mg/dl nella popolazione modificata intent-to-treat (mITT) 8. Proporzione di pazienti che raggiungono un livello di non-HDL-C <100 mg/dl nella popolazione modificata intent-to-treat (mITT). Percentuale di pazienti che raggiungono un livello di non HDL-C <80 mg/dl nella popolazione modificata intent-to-treat (mITT) 9. Variazione percentuale del livello di Lp(a) nella popolazione intent-to-treat (ITT). Variazione percentuale del livello di HDL-C nella popolazione intent-to-treat (ITT). 10. Variazione percentuale del livello di TG nella popolazione intent-to-treat (ITT). Variazione percentuale del numero di particelle di LDL-C nella popolazione intent-to-treat (ITT). Variazione percentuale della dimensione delle particelle di LDL-C nella popolazione intent-to-treat (ITT).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- From baseline to Week 24 2- From baseline to Weeks 12 and 24 3- From baseline to Week 12 4-5-6- From baseline to Week 24 7-8- Week 24 9-10- From baseline to Week 24
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1 Dal basale alla settimana 24 2 Dal basale alle settimane 12 e 24 3 Dal basale alla settimana 12 4-5-6 Dal basale alla settimana 24 7-8 Alla Settimana 24 9-10 Dal basale alla settimana 24
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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 | No |
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 | 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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 |
United States |
Austria |
Finland |
France |
Germany |
Greece |
Italy |
Spain |
Switzerland |
United Kingdom |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |