A randomized study of the relative pharmacokinetics, pharmacodynamics, and safety of alirocumab, a fully human monoclonal antibody to PCSK9, after single subcutaneous administration at three different injection sites in healthy subjects

Catherine Lunven, Tobias Paehler, Franck Poitiers, Aurélie Brunet, Jacques Rey, Corinne Hanotin, William J Sasiela, Catherine Lunven, Tobias Paehler, Franck Poitiers, Aurélie Brunet, Jacques Rey, Corinne Hanotin, William J Sasiela

Abstract

Aims: We investigated the relative pharmacokinetics, pharmacodynamics, and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab following injection at three different sites.

Methods: Sixty healthy subjects (39 male, 21 female; age 20-45 years) were randomized to receive a single subcutaneous injection of alirocumab 75 mg via 1-mL prefilled pen into the abdomen, upper arm, or thigh (NCT01785329). Subjects were followed for 85 days ± 2 days following study drug administration. Pharmacokinetic (PK) parameters for the systemic exposure of alirocumab were calculated, and levels of free PCSK9 were assessed. Percentage changes from baseline in LDL-C were compared between injection site groups using linear mixed-effects models.

Results: Alirocumab concentration-time profiles were similar, and free PCSK9 levels were reduced to approximately zero between Day 3 and Day 4 postinjection in all groups. LDL-C levels reached nadir on Day 15 postinjection in all groups with mean percentage reductions of 48.4% (abdomen), 39.5% (upper arm), and 45.6% (thigh) at this time point. A similar effect on LDL-C levels was seen across the entire time course of the study at all three injection sites. Treatment-emergent adverse events were experienced by 8/20 (abdomen), 11/20 (upper arm), and 13/20 (thigh) subjects. There were 2 mild/transient injection site reactions. There were no serious adverse events.

Discussion: A single subcutaneous administration of alirocumab 75 mg via prefilled pen was well tolerated with similar pharmacokinetics and pharmacodynamics when injected into the abdomen, upper arm, or thigh.

Conclusion: These results suggest that alirocumab can be interchangeably injected in the abdomen, upper arm, or thigh.

Keywords: Alirocumab; Cholesterol; Low-density lipoprotein; Pharmacodynamics; Pharmacokinetics; Proprotein convertase subtilisin/kexin type 9.

© 2014 Sanofi and Regeneron Pharmaceuticals Inc. Cardiovascular Therapeutics published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Mean (SD) alirocumab concentration (A), free PCSK9 levels (B), and percentage change in LDL-C from baseline (C) after subcutaneous administration of alirocumab 75 mg. LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9; SEM, standard error of the mean; SD, standard deviation.

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Source: PubMed

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