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Pharmacokinetics and pharmacodynamics of a pasireotide subcutaneous depot (CAM4071) and comparison with immediate and long-acting release pasireotide

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Abstract

Purpose

To assess the pharmacokinetics, pharmacodynamics, safety and tolerability of subcutaneous depot CAM4071, a novel, ready-to-use pasireotide formulation.

Methods

This was a phase 1, randomised, open-label study in healthy volunteers. After a single 600 µg dose of pasireotide immediate release (IR), participants were randomised to one of eight groups to receive either a CAM4071 upper thigh (5, 10, 20, 40 or 80 mg) or buttock (20 mg) injection or multiple pasireotide IR 900 µg upper thigh injections twice daily or a single pasireotide long-acting release (LAR) 60 mg intramuscular buttock injection.

Results

Ninety-four participants were randomised. For all CAM4071 doses, initial pasireotide release was relatively rapid compared to pasireotide LAR and sustained over the 2-month observation period, with a slow decay in plasma concentrations. CAM4071 maximum plasma concentrations increased slightly greater than dose proportionally; area under the curve extrapolated to infinity increased approximately dose proportionally. Relative bioavailability of pasireotide for different doses of CAM4071 versus pasireotide IR 600 μg ranged from 0.752 (90% confidence interval [CI]: 0.58, 0.98) to 1.68 (1.32, 2.14), and versus pasireotide LAR: 0.517 (0.37, 0.72) to 1.15 (0.84, 1.58). CAM4071 doses >5 mg exhibited rapid initial reductions of insulin-like growth factor 1 (IGF-1) compared to pasireotide LAR. Maximum IGF-1 inhibition was greatest for CAM4071 80 mg. CAM4071 injections ≤40 mg were well tolerated and comparable with currently available pasireotide formulations.

Conclusion

CAM4071 provided long-acting release of pasireotide over at least one month, with high bioavailability and onset and duration of IGF-1 suppression similar to pasireotide LAR.

Trial registration

EudraCT: 2014-003783-20.

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Acknowledgements

The authors thank the volunteers, the investigators and their teams who took part in this study and the clinical trial that the data were based on. The authors also acknowledge Harry Smith, MSc, Sunandan Dhar, MTech, and James Evry, MSc, Costello Medical, UK, for medical writing and editorial assistance based on the authors’ input and direction. This study was sponsored by Camurus AB.

Funding

This analysis was sponsored by Camurus AB. Support for third-party writing assistance for this article, provided by Harry Smith, MSc, Sunandan Dhar, MTech, and James Evry, MSc, Costello Medical, UK, was funded by Camurus AB in accordance with Good Publication Practice 2022 guidelines (GPP 2022 [ismpp.org]).

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Authors and Affiliations

  1. Camurus AB, Lund, Sweden

    Markus Johnsson, Alberto M. Pedroncelli, Anna Hansson & Fredrik Tiberg

Authors
  1. Markus Johnsson
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  2. Alberto M. Pedroncelli
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  3. Anna Hansson
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Contributions

F.T., A.M.P. and M.J. made substantial contributions to the study conception and design. F.T., A.M.P., M.J. and A.H. made substantial contributions to analysis and interpretation of the data. All authors draughted the article or revised it critically for important intellectual content. All authors approved the final version of the article to be published.

Corresponding author

Correspondence to Fredrik Tiberg.

Ethics declarations

Conflict of interest

F.T., A.M.P., M.J. and A.H. are current employees of Camurus AB.

Ethics approval

This trial was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki and in compliance with the approved protocol, Guidelines of the International Council for Harmonisation on Good Clinical Practice and applicable regulatory requirements. The study was approved by an independent ethics committee (Ethics Committee of the State of Berlin), approval number 14/0518 – EK 13.

Consent to participate

Written informed consent was obtained from all participants included in the study.

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All the results presented in this article are in aggregate form, and no personally identifiable information was used for this study.

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Johnsson, M., Pedroncelli, A.M., Hansson, A. et al. Pharmacokinetics and pharmacodynamics of a pasireotide subcutaneous depot (CAM4071) and comparison with immediate and long-acting release pasireotide. Endocrine (2024). https://doi.org/10.1007/s12020-024-03741-3

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