Background
Methods
Study design
Inclusion and exclusion criteria
Inclusion criteria |
Aged ≥18 years or legal age of majority at screening visit, whichever is greater |
ASCVD (including CHDa, documented PAD or previous ischaemic stroke) and/or ≥1 additional cardiovascular risk factorb
|
Stable anti-hyperglycaemic treatment (including insulin) |
Stable, maximally tolerated dose/regimen of statin for at least 4 weeks prior to screening without other lipid-lowering therapy |
Non-HDL-C ≥100 mg/dl (2.59 mmol/l) |
TG ≥150 and <500 mg/dl (≥1.70 and <5.65 mmol/l) |
No weight variation >5 kg within 3 months |
Exclusion criteria |
HbA1c ≥9% |
Use of any lipid-lowering therapy (other than statin) or over-the-counter product/nutraceuticals known to impact lipids within 4 weeks prior to screening |
BMI >45 kg/m2
|
Alcohol consumption >two standard alcoholic drinks/day |
Study procedures
Endpoints and assessments
Primary endpoint |
Change (%) in non-HDL-C from baseline to week 24 in ITT population |
Key secondary efficacy endpoints |
Change (%) from baseline in ITT population |
Measured LDL-C at week 24 |
Non-HDL-C at week 12 |
Measured LDL-C at week 12 |
Apo B at week 24 |
TC at week 24 |
Lp(a) at week 24 |
TGs at week 24 |
HDL-C at week 24 |
LDL-P number at week 24 |
Other efficacy endpoints |
Change (%) from baseline in ITT population |
Calculated LDL-C at weeks 12 and 24 |
Apo B, TC, Lp(a), HDL-C, TG, and LDL particle number at week 12 |
Apo A-1, Apo C-III, TRL, LDL-P size, VLDL, HDL and IDL particle number at weeks 12 and 24 |
Measured LDL-C and TG according to baseline TG (<median or >median) at weeks 12 and 24 |
Patients (%) reaching |
Measured LDL-C <50, 70 and 100 mg/dl at weeks 12 and 24 |
Non-HDL-C <80, 100 and 130 mg/dl at weeks 12 and 24 |
≥50% reduction from baseline in measured LDL-C at weeks 12 and 24 |
Apo B <80 mg/dl at weeks 12 and 24 |
Absolute change from baseline in Apo B/Apo A-1, TC/HDL-C and LDL-C/HDL-C ratios at weeks 12 and 24 |
Diabetes-related endpoints |
Absolute change from baseline to weeks 12 and 24 in ITT population |
HbA1c
|
FPG |
Number of glucose-lowering agents |
Safety endpoints |
TEAEs |
AESIs |
Product complaints |
Laboratory data (including microalbuminuria) |
Vital signs (including change in body weight and BMI) |
Questionnaire |
Treatment acceptance (I-TAQ) at weeks 8 and 24 (for alirocumab arm onlya) |
Other endpoints |
Total and free PCSK9 levels at baseline, weeks 12 and 24 |
Anti-alirocumab antibodies |