At screening, patients either had LDL C 70 mg dL with documented CVD or LDL C 100 mg dL with no documented his tory of CVD. The maximum tolerated dose of statin was defined as either rosuvastatin 20 mg or 40 mg daily, atorvastatin 40 mg or 80 mg daily, or simvastatin 80 mg daily. However, patients not able to tolerate the above statin doses remained eligible Sorafenib Tosylate clinical trial for inclusion if they were on a lower dose of daily ator vastatin, rosuvastatin, or simvastatin provided that the investigator had a documented reason for not using the higher dose. Study procedures Patients meeting the inclusion criteria entered a screen ing period of up to 2 or 3 weeks prior to randomization. During screening, pa tients completed informed consent, inclusion exclusion criteria were further assessed, patient information was collected, and patients were trained in the use of the auto injector device.

In addition, vital signs were taken, a 12 lead electrocardiogram was performed, and fasting blood and urine samples were obtained for analysis. AEs will be assessed from the screening visit throughout the study. LDL C will be calculated using the Friedewald formula at screening and at all time points during the double blind treatment periods. If TGs exceed 400 mg dL then the central laboratory will reflexively measure LDL C ra ther than calculating it. LDL C will also be measured at week 0 and week 24. Other lipid parameters, including total cholesterol, HDL C, TGs, Apo B, Apo A1, and Lp, will be mea sured directly by the central laboratory.

COMBO I Eligible patients were randomized, with stratification by 1 prior history of myocar dial infarction or ischemic stroke, and 2 intensity of statin treatment, to ensure balance between arms for these factors. After randomization, patients entered a double blind treatment period of 52 weeks. In addition to existing statin and other existing LLT if appropriate, patients randomized to alirocumab received a 75 mg subcutaneous dose every 2 weeks, adminis sellckchem tered as a single 1 mL injection utilizing an auto injector, from randomization to week 12. Patients randomized to placebo received a 1 mL SC placebo injection from an identical auto injector. At week 12, patients randomized to alirocumab were up titrated to 150 mg Q2W if the week 8 LDL C was 70 mg dL. To maintain blinding, the patient and investigator were not informed of the week 8 LDL C levels, continuation or up titration of dose occurred in an auto mated and blinded manner. The 150 mg Q2W dose of alirocumab was also administered as a 1 mL solution in an auto injector.