Bococizumab is a humanized monoclonal antibody binding proprotein convertase subtilisin/kexin type 9, which may be a potential therapeutic option for reducing low-density lipoprotein cholesterol (LDL-C) levels in patients with hypercholesterolemia. In this 24-week, multicenter, double-blind, placebo-controlled, dose-ranging study (NCT01592240), subjects with LDL-C levels≥80 mg/dl on stable statin therapy were randomized to Q14 days subcutaneous placebo or bococizumab 50, 100, or 150 mg or Q28 days subcutaneous placebo or bococizumab 200 or 300 mg. Doses of bococizumab were reduced if LDL-C levels persistently decreased to ≤25 mg/dl. The primary end point was the absolute change in LDL-C levels from baseline to week 12 after placebo or bococizumab administration. Continuation of bococizumab administration through to week 24 enabled the collection of safety data over an extended period. Of the 354 subjects randomized, 351 received treatment (placebo [n=100] or bococizumab [n=251]). The most efficacious bococizumab doses were 150 mg Q14 days and 300 mg Q28 days. Compared with placebo, bococizumab 150 mg Q14 days reduced LDL-C at week 12 by 53.4 mg/dl and bococizumab 300 mg Q28 days reduced LDL-C by 44.9 mg/dl; this was despite dose reductions in 32.5% and 34.2% of subjects at week 10 or 8, respectively. Pharmacokinetic/pharmacodynamic model-based simulation assuming no dose reductions predicted that bococizumab would lower LDL-C levels by 72.2 and 55.4 mg/dl, respectively. Adverse events were similar across placebo and bococizumab groups. Few subjects (n=7; 2%) discontinued treatment because of treatment-related adverse events. In conclusion, bococizumab significantly reduced LDL-C across all doses despite dose reductions in many subjects. Model-based simulations predicted greater LDL-C reduction in the absence of bococizumab dose reduction. The Q14 days regimen is being evaluated in phase 3 clinical trials.