Rationale and Design of LAPLACE‐2: A Phase 3, Randomized, Double‐Blind, Placebo‐ and Ezetimibe‐Controlled Trial Evaluating the Efficacy and Safety of Evolocumab in Subjects With Hypercholesterolemia on Background Statin Therapy

ABSTRACT Low‐density lipoprotein cholesterol (LDL‐C) levels are significantly associated with atherosclerotic cardiovascular disease (ASCVD) risk, and studies using interventions that lower LDL‐C levels have been shown to reduce the risk of ASCVD events and mortality. Statin treatment is the current first‐line therapy for lowering LDL‐C and reducing ASCVD risk. However, many patients are still unable to reach recommended LDL‐C goals on maximally tolerated statin therapy. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, including evolocumab (previously AMG 145), dramatically lowered LDL‐C in phase 2 clinical trials when administered alone or in combination with a statin. The aim of this phase 3 study is to evaluate the efficacy of 12 weeks of subcutaneous evolocumab (vs placebo) administered every 2 weeks or every month in combination with a statin in patients with hypercholesterolemia and mixed dyslipidemia. This study will also provide comparative efficacy, safety, and tolerability data between evolocumab and ezetimibe when added to background atorvastatin therapy.