Cancer Res Treat.  2016 Jul;48(3):1120-1129. 10.4143/crt.2015.436.

A Multi-centric Bioequivalence Trial in Ph+ Chronic Myeloid Leukemia Patients to Assess Bioequivalence and Safety Evaluation of Generic Imatinib Mesylate 400 mg Tablets

• Arora R
• Sharma M
• Monif T
• Iyer S

• KMID: 2344086
• DOI: http://doi.org/10.4143/crt.2015.436

Abstract

PURPOSE
This study was designed to characterize the pharmacokinetic profile and to assess bioequivalence of the sponsor's test formulation (imatinib mesylate 400 mg tablets) with an innovator product (Gleevec 400 mg tablets, Novartis Pharmaceuticals) under fed conditions, in adult patients of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) stabilized on imatinib mesylate 400 mg. In addition, the aim of this study was to monitor the safety profile of investigational medicinal products (IMPs).
MATERIALS AND METHODS
A multicenter, randomized, open label, two-period, crossover, single dose bioequivalence study was designed for conduct under fed conditions in 42 adult Ph+ CML patients already stabilized on imatinib 400 mg tablets. Pharmacokinetic parameters Tmax, Cmax, and AUC0-24 were calculated using a non-compartmental model on validated WinNonlin software. Validated SAS software was used for statistical evaluation of data. The safety profile of investigational products was monitored during the course of study by applying a clinical process for recording observed untoward effects postadministration of investigational products.
RESULTS
The 90% confidence intervals for the test/reference mean ratios of the ln-transformed PK variables Cmax (99.0%) and AUC0-24 (99.2%) were within an acceptable range of 80%-125%, as per bioequivalence assumptions. Both formulations were well tolerated after oral administration of IMPs.
CONCLUSION
The test product was found to be bioequivalent and safe, and thus can be used interchangeably in clinical practice.

Keyword

Imatinib mesylate; Pharmacokinetics; Therapeutic equivalency; Safety; Leukemia

MeSH Terms

Administration, Oral
Adult
Humans
Imatinib Mesylate*
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive*
Mesylates
Pharmacokinetics
Philadelphia Chromosome
Tablets*
Therapeutic Equivalency*
Imatinib Mesylate
Mesylates
Tablets

Figure

• 

  Fig. 1. Plasma drug concentration verses time profiles of test and reference product of imatinib mesylate 400 mg tablets in Philadelphia chromosome positive chronic myeloid leukemia patients (n=40).

Reference

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