A randomized pharmacokinetic/pharmacodynamic study comparing the bioequivalence of potential biosimilar candidate P044 with reference medicine in healthy volunteers

ABSTRACT

Background

P044 is a proposed biosimilar candidate of Teriparatide for reference medicine, Forsteo®. This study was designed to evaluate the Pharmacokinetic/Pharmacodynamic (PK/PD) bioequivalence between P044 and Forsteo®.

Methods

In this randomized, open-label, single-dose, crossover study, 66 healthy female subjects were randomized to receive P044 and Forsteo®. The primary PK endpoints of the study were the area under the concentration versus time from zero to infinity (AUC_0-inf) and maximum plasma concentration (C_max). Secondary endpoints included area under the concentration versus time from zero to the last quantifiable concentration (AUC_0-last) and C_max for PD parameter, additional PK parameters and safety.

Results

Sixty-six subjects were enrolled in the study and baseline demographics were similar between the two treatments. The two treatments presented similar PK/PD parameters and the 90% confidence interval for primary and secondary endpoints were within the bioequivalence acceptance range (80.00–125.00%) for all parameters. None of the subjects experienced serious adverse event, and all of the reported adverse events were mild and similar between two treatments.

Conclusions

This study demonstrated the PK/PD similarity of P044 to reference medicine, Forsteo® and safety profiles were comparable between treatments.

Trial Registration

EudraCT Number: 2019–004477-82

KEYWORDS:

• Bioequivalence
• biosimilar
• pharmacokinetics
• pharmacodynamic
• teriparatide

Acknowledgments

The authors would like to thank all those involved in this study and Comac Medical Ltd. as the CRO who conducted the study and special thanks to Tsvetelina Ivanova and Katerina Markoska from Comac Medical Ltd. team for their contribution in the study. Parnian Maghzi and Borna Payandemehr from sponsor team is deeply acknowledged for their insight and contributions to the development of this work and Seyed Hossein Seyedagha from sponsor team for his contribution in reanalysis of statistical data.

Declaration of interest

Morteza Azhdarzadeh and Mohammad Farmahini Farahani are employees of the Sponsor and have no other conflicts of interest to disclose. The other authors are employees of Comac Medical Ltd., the contract research organization that was contracted by the sponsor to carry out the research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contributions

All authors of the paper agree to be accountable for all parts of the study including the design, review of documents, and implementation of the trial. Furthermore, all authors were involved in revising the manuscript and approval of the final version to be published. Dr. Ekaterina Raykova was the principal investigator for this study, and he had direct clinical responsibility for volunteers.

Data Availability Statement

The datasets generated during and/or analysed in the current study are available from the corresponding author on reasonable request but remain subject to all applicable legal requirements to protect the confidentiality of the study participants’ personal information.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This study was fully funded by CinnaGen Co.