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 Cmax. 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 Cmax 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.