E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.1 |
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.
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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). |
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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.
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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).
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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 |
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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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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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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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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 | 4 |
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 | 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 |
Austria |
Belgium |
Brazil |
France |
Germany |
Italy |
Netherlands |
Spain |
Switzerland |
United Kingdom |
United States |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
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 |