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

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.

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Key information

Conditions

Healthy

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Healthy subjects
BMI between 18.5 and 30 kg/m2
Body mass > 60 kg
Non-tobacco user
Written consent given for participation in the study

Exclusion criteria

Evidence of clinically relevant oral, cardiovascular, hematologic, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric or skin disorder
Heavy alcohol consumption and regular exposure to drug of abuse

Treatment and study plan

Zeneo® - Methotrexate

Other

0.625 mL of methotrexate solution 40 mg/ML for subcutaneous injection with a prefilled and needle-free delivery system

Methotrexate Biodim®

Drug

1 mL of methotrexate solution 25 mg/mL for subcutaneous injection with a conventional needle and syringe injection

Primary outcomes

Maximum observed plasma concentration (Cmax).

Time frame: serial pharmacokinetic plasma concentrations were drawn prior pre-dose and post-dose at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Area under the plasma concentration versus time curve (AUC) time zero to time of the last quantifiable concentration (AUC(0-t)).

Time frame: serial pharmacokinetic plasma concentrations were drawn prior pre-dose and post-dose at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours

Sponsors and collaborators

Lead sponsor

Crossject

Industry

Registry information

Official study title

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.

Important dates

Study start: 2014
Primary completion: 2014
Study completion: 2014
First posted: Apr 6, 2017
Registry last updated: Feb 16, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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