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Bioequivalence of Canakinumab Liquid Pre-Filled Syringe and Reconstituted Lyophilized Formulations Following 150 mg Subcutaneous Administration: A Randomized Study In Healthy Subjects

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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 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.

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Acknowledgments

Andrea Chioato, Emanuele Noseda, Laurence Colin, Ralph Matott, Andrej Skerjanec, Albert J. Dietz are employees of Novartis Pharma AG, Switzerland and have participated in the preparation of the manuscript. This study and the manuscript were funded by Novartis Pharma AG, Switzerland.

Conflict of interest

A. Chioato and E. Noseda are Novartis employee. A. Skerjanec is a employee of Novartis. L. Colin is at Novartis Pharma AG. R. Matott work for the sponsor.

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Authors and Affiliations

  1. Novartis Institutes for BioMedical Research, Translational Medicine, 4002, Basel, Switzerland

    Andrea Chioato, Emanuele Noseda, Laurence Colin, Ralph Matott & Andrej Skerjanec

  2. Spaulding Clinical, LLC, West Bend, WI, USA

    Albert J. Dietz

Authors
  1. Andrea Chioato
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  2. Emanuele Noseda
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  3. Laurence Colin
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  4. Ralph Matott
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  5. Andrej Skerjanec
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  6. Albert J. Dietz
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Corresponding author

Correspondence to Andrea Chioato.

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Chioato, A., Noseda, E., Colin, L. et al. Bioequivalence of Canakinumab Liquid Pre-Filled Syringe and Reconstituted Lyophilized Formulations Following 150 mg Subcutaneous Administration: A Randomized Study In Healthy Subjects. Clin Drug Investig 33, 801–808 (2013). https://doi.org/10.1007/s40261-013-0127-4

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  • DOI: https://doi.org/10.1007/s40261-013-0127-4

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