Single-center, single-dose, open-label, randomized, two-period crossover study on the bioavailability of methotrexate administered using a novel prefilled, needle-free delivery system

Abstract

Objective: Zeneo¹ is a needle-free injection device. We performed a pharmacokinetic study to investigate the bioequivalence of methotrexate administered subcutaneously using either the needle-free injection device or a conventional needle and syringe.

Research design and methods: This was a single-dose, open-label, laboratory-blind, randomized crossover study performed in adult healthy volunteers. Each participant received two methotrexate injections (each 25 mg), one via needle-free injection device and one via conventional injection, with a 21–28 day wash-out interval between dosing. For each participant, the administration site for both injections was either the abdomen or the thigh.

Main outcome measures: The primary pharmacokinetic outcome parameters were AUC_(0–t) and C_max. Bioequivalence was assessed by standard criteria: whether 90% confidence intervals of geometric mean ratios for the two administration methods were within 80–125%.

Results: Fifty-two individuals completed the study. Bioequivalence criteria were met for AUC_(0–t), for the overall analysis (both injection sites: 90% confidence interval: 99.4–103.1%), and for each injection site separately. Bioequivalence was similarly demonstrated with AUC_(0–∞). Bioequivalence criteria for C_max were fulfilled for abdominal administration but not for the overall analysis. Injection via the needle-free injection device was well tolerated.

Limitations: Limitations include conducting the study in healthy volunteers and the relatively small subject number (albeit satisfactory for bioequivalence).

Conclusions: This study shows that methotrexate injection via needle-free injection device is bioequivalent to a conventional needle and syringe in relation to AUC_(0–t) and AUC_(0–∞). Studies of needle-free injection device use in patients requiring methotrexate therapy are planned.

Keywords:

• Autoinjector
• bioequivalence
• methotrexate
• pharmacokinetics

Notes

Transparency

Declaration of funding

This study was funded by Crossject SA.

Declaration of financial/other relationships

B.B. has disclosed that he was employed by Crossject as a sponsored medical expert for this study. J.-E.G. has disclosed that he has received honoraria and research grants from Abbvie, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche and UCB. A.A. and C.V. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Medical writing support was provided by Newmed Publishing Services, with funding from Crossject SA. The authors would also wish to thank Christelle Foucher for assistance with additional analyses.

Notes

1 Zeneo is a registered trade name of Crossject, Chenôve, France

2 Biodim is a registered trade name of Laboratoire Biodim, Paris, France

3 Phoenix and WinNonlin are registered trade names of Certara LP, St Louis, MO, USA