Bioequivalence of canakinumab liquid pre-filled syringe and reconstituted
lyophilized formulations following 150 mg subcutaneous administration: a
randomized study in healthy subjects.
Author(s): Chioato A(1), Noseda E, Colin L, Matott R, Skerjanec A, Dietz AJ.
Affiliation(s): Author information:
(1)Novartis Institutes for BioMedical Research, Translational Medicine, 4002, Basel,
Switzerland, andrea.chioato@novartis.com.
Publication date & source: 2013, Clin Drug Investig. , 33(11):801-8
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.
CONCLUSION: The 150 mg liquid pre-filled syringe and lyophilized formulations of
canakinumab are bioequivalent.
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