title: A Multi-centric Bioequivalence Trial in Ph+ Chronic Myeloid Leukemia Patients to Assess Bioequivalence and Safety Evaluation of Generic Imatinib Mesylate 400 mg Tablets.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  The test product was found to be bioequivalent and safe, and thus can be used interchangeably in clinical practice.
authors.affiliation: Faculty of Pharmacy, Jamia Hamdard, Hamdard University, New Delhi, India.|Clinical Pharmacology and Pharmacokinetics, Sun Pharmaceutical Industries Limited, Gurgaon, Haryana, India.
authors.forename: Rachna
authors.initials: R
authors.lastname: Arora
authors.affiliation: Faculty of Pharmacy, Jamia Hamdard, Hamdard University, New Delhi, India.
authors.forename: Manju
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Clinical Pharmacology and Pharmacokinetics, Sun Pharmaceutical Industries Limited, Gurgaon, Haryana, India.
authors.forename: Tausif
authors.initials: T
authors.lastname: Monif
authors.affiliation: Clinical Pharmacology and Pharmacokinetics, Sun Pharmaceutical Industries Limited, Gurgaon, Haryana, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Iyer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D000970:Antineoplastic Agents; D016568:Drugs, Generic; D047428:Protein Kinase Inhibitors; D013607:Tablets; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases
keywords: Imatinib mesylate; Leukemia; Pharmacokinetics; Safety; Therapeutic equivalency