Bioequivalence of canakinumab liquid pre-filled syringe and reconstituted lyophilized formulations following 150 mg subcutaneous administration: A randomized study in healthy subjects

摘要

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 AUClast (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 AUClast were similar for the two formulations. The geometric mean ratio (pre-filled syringe vs. lyophilized form) of C max and AUClast 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.