title: Bioequivalence of canakinumab liquid pre-filled syringe and reconstituted lyophilized formulations following 150 mg subcutaneous administration: a randomized study in healthy subjects.
abstract: BACKGROUND
  Canakinumab is a human anti-interleukin-1beta antibody approved for the treatment of cryopyrin associated periodic syndrome currently formulated as a lyophilized powder requiring reconstitution. A new formulation (solution for injection as pre-filled syringe) has been developed to avoid reconstitution.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the bioequivalence of pre-filled syringe and reconstituted formulations following 150 mg administration in healthy subjects.
  
  
  METHODS
  This was an open-labeled, randomized, single dose, parallel-group study in 130 healthy subjects, followed for 120 days. Subjects received a single subcutaneous injection of 150 mg canakinumab after either reconstitution or in pre-filled syringe formulation, followed by pharmacokinetics/pharmacodynamics evaluations and safety assessments. The main outcome measure for the study was the pharmacokinetic bioequivalence of the two formulations, which was concluded if the 90% confidence intervals for the ratios of AUC(last) (area under the serum concentration-time curve from time zero to time of last measurable concentration) and C(max) (maximum serum concentration) were entirely contained within the interval, 0.80-1.25.
  
  
  RESULTS
  The arithmetic mean values for the exposure parameters C(max) and AUC(last) were similar for the two formulations. The geometric mean ratio (pre-filled syringe vs. lyophilized form) of C(max) and AUC(last) were 0.99 and 1.01. The associated 90% confidence intervals were 0.90 to 1.08 and 0.94 to 1.09, respectively. Most common adverse events were headache and nasopharyngitis. Neutropenia occurred in 2 cases (reported as serious adverse events). No deaths occurred.
  
  
  CONCLUSIONS
  The 150 mg liquid pre-filled syringe and lyophilized formulations of canakinumab are bioequivalent.
authors.affiliation: Novartis Institutes for BioMedical Research, Translational Medicine, 4002, Basel, Switzerland, andrea.chioato@novartis.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chioato
authors.forename: Emanuele
authors.initials: E
authors.lastname: Noseda
authors.forename: Laurence
authors.initials: L
authors.lastname: Colin
authors.forename: Ralph
authors.initials: R
authors.lastname: Matott
authors.forename: Andrej
authors.initials: A
authors.lastname: Skerjanec
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Dietz
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D005612:Freeze Drying; D006801:Humans; D007279:Injections, Subcutaneous; D053583:Interleukin-1beta / Q000378:metabolism; D012016:Reference Values; D013594:Syringes; D013810:Therapeutic Equivalency
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053583:Interleukin-1beta; C541220:canakinumab
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