Pharmacokinetic/pharmacodynamic and safety study of a single dose of evolocumab 140 mg in healthy Chinese subjects

Objective: Evolocumab, a human monoclonal antibody that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9), markedly reduces low-density lipoprotein cholesterol (LDL-C). Here we characterize the pharmacokinetics, pharmacodynamics. safety, and tolerability of evolocumab manufactured at a new site administered in healthy Chinese subjects. ULterials and methods: This phase 1 study of a single subcutaneous 140-mg dose of evolocumab was conducted in healthy subjects of Chinese descent residing in Hong Kong. Subjects were followed through day 85.1 sults: 20 subjects (all men) were enrolled. Mean (SD) age was 26.6 (8.5) years; baseline LDL-C was 2.4 (0.7) mmol/L. Mean (SD) evolocumab maximum serum concentration (C-max) was 14.1 (5.0) mu g/mL; area under the serum drug concentration-time curve from time 0 to time of last quantifiable concentration (AUC(last)) was 178 (80) day x mu g/mL; AUC from time 0 to infinity (AUC(inf)) was 187 (80) day x mu g/mL; terminal half-life was 5.95 (1.76) days; median time to reach C-max (t(max)) was 4.0 days. Maximum LDL-C decrease (-57.5%) was observed on day 15 and recovered to baseline by day 57. The most common adverse events (AEs) were nasal congestion (20%), oropharyngeal pain (15%), sneezing (15%), cough (10%), upper respiratory tract infection (10%), and diarrhea (10%). Most AEs were isolated incidences of mild severity, with no serious or treatment-related events. No anti-evolocumab antibodies were detected. Conclusion: A single 140-mg dose of evolocumab manufactured at the new site and administered in healthy Chinese subjects was associated with typical antibody pharmacokinetics, rapid and reversible decreases in LDL-C, and no new safety events.