title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  These results suggest that alirocumab can be interchangeably injected in the abdomen, upper arm, or thigh.
authors.affiliation: Sanofi, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lunven
authors.forename: Tobias
authors.initials: T
authors.lastname: Paehler
authors.forename: Franck
authors.initials: F
authors.lastname: Poitiers
authors.forename: Aurélie
authors.initials: A
authors.lastname: Brunet
authors.forename: Jacques
authors.initials: J
authors.lastname: Rey
authors.forename: Corinne
authors.initials: C
authors.lastname: Hanotin
authors.forename: William J
authors.initials: WJ
authors.lastname: Sasiela
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors* / Q000097:blood; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C571059:alirocumab
keywords: Alirocumab; Cholesterol; Low-density lipoprotein; Pharmacodynamics; Pharmacokinetics; Proprotein convertase subtilisin/kexin type 9