Journal
INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
Volume 57, Issue 12, Pages 575-589Publisher
DUSTRI-VERLAG DR KARL FEISTLE
DOI: 10.5414/CP203418
Keywords
bococizumab; Japanese; PCSK9 inhibitor; pharmacokinetics; biomarker
Categories
Funding
- Pfizer
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Objective: Bococizumab, a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, has been shown to reduce low-density lipoprotein cholesterol (LDL-C). Here, we describe the pharmacokinetics and pharmacodynamics of bococizumab and its effect on lipoprotein particle composition and other biomarkers, based on a double-blind, placebo-controlled, randomized, dose-ranging study. Materials and methods: The study consisted of two populations: Japanese subjects with uncontrolled LDL-C (LDL-C >= 100 mg/dL) despite treatment with atorvastatin (n = 121) and Japanese subjects naive to lipid-lowering agents with LDL-C >= 130 mg/dL (n = 97). Subjects were randomized to receive either bococizumab 50, 100, or 150 mg or placebo, every 2 weeks. One arm of subjects in the ator-vastatin-treated population received ezetimibe 10 mg instead of bococizumab. Results: In both populations, bococizumab exposure increased with increasing dose, and subjects with lower body weights tended to have higher exposures. Bococizumab treatment was associated with a dose-dependent reduction in LDL particles and a small increase in total high-density lipoprotein (HDL) particles. Significant reductions in lipoprotein-associated phospholipase A2 (Lp-PLA2) were observed for bococizumab-treated subjects but not for subjects treated with placebo or ezetimibe. Conclusion: Increased bococizumab dosage resulted in increased exposure. Levels of LDL and HDL particles and biomarkers such as Lp-PLA2 were also altered with bococizumab treatment.
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