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

Crossject

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Other: Zeneo® - Methotrexate; Drug: Methotrexate Biodim®

Study type: Interventional

Funder types: Industry

Identifiers

NCT03103334

L9-E-CJT-CM-131003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 58 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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58 participants in 4 patient groups

Experimental A

Experimental group

Description:

Zeneo® - Methotrexate thigh to Methotrexate Biodim® thigh

Treatment:

Drug: Methotrexate Biodim®

Other: Zeneo® - Methotrexate

Experimental B

Experimental group

Description:

Methotrexate Biodim® thigh to Zeneo® - Methotrexate thigh

Treatment:

Drug: Methotrexate Biodim®

Other: Zeneo® - Methotrexate

Experimental C

Experimental group

Description:

Zeneo® - Methotrexate abdomen to Methotrexate Biodim® abdomen

Treatment:

Drug: Methotrexate Biodim®

Other: Zeneo® - Methotrexate

Experimental D

Experimental group

Description:

Methotrexate Biodim® abdomen to Zeneo® - Methotrexate abdomen

Treatment:

Drug: Methotrexate Biodim®

Other: Zeneo® - Methotrexate