NCT03103334

A Bioavailability Study of Methotrexate 25 mg Administered by Needle Injection and a Pre Filled Needle-free Device in Healthy Volunteers.

A Single Center Single Dose Open-label Randomized Two Period Crossover Study to Determine the Bioavailability of Two Formulations of Methotrexate 25 mg Administered by Needle Injection and a Pre-filled Needle-free Device in at Least 48 Healthy Volunteers.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 58 (actual)
• Sponsor: Crossject · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The objective is to determine whether the test product, Methotrexate 40 mg/mL solution for injection administered subcutaneously by the prefilled and needle-free delivery system Zeneo®, and the reference product, Methotrexate Biodim® 25 mg/mL, solution for injection administered subcutaneously by a conventional syringe with needle are bioequivalent.

Detailed description

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 25mg), 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(0-1). 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(0-1). Studies of needle-free injection device use in patients requiring methotrexate therapy are planned.

Conditions

• Healthy

Interventions

Type	Name	Description
OTHER	Zeneo® - Methotrexate	0.625 mL of methotrexate solution 40 mg/ML for subcutaneous injection with a prefilled and needle-free delivery system
DRUG	Methotrexate Biodim®	1 mL of methotrexate solution 25 mg/mL for subcutaneous injection with a conventional needle and syringe injection

Timeline

• Start date: 2014-06-01
• Primary completion: 2014-09-01
• Completion: 2014-12-01
• First posted: 2017-04-06
• Last updated: 2021-02-16