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

Immunoglobulin G4 (IgG4)–related diseases are a spectrum of systemic inflammatory conditions of unknown etiology, which are characterized by infiltration of tissues by IgG4 plasma cells and sclerosing inflammation (Cheuk and Chan Adv Anat Pathol 17:303-32, 2010). Although this condition was initially described in relation to autoimmune pancreatitis, now it has been reported in almost every organ system of body (Zen and Nakanuma Am J Surg Pathol 34:1812-9, 2010, Masaki et al. Ann Rheuma Dis 68:1310-5, 2009). Orbital involvement by IgG4 disease can involve extraocular muscles (EOM), lacrimal glands, conjunctiva, eyelids, infraorbital nerve, orbital fat, and nasolacrimal system (McNab and McKelvie. Ophthal Plast Reconstr Surg 31:167-78, 2015, Katsura et al. Neuroradiology 54:873-82, 2012). The basis of using ⁶⁸Ga-DOTANOC PET/CT in IgG4 orbital disease is the known expression of somatostatin receptors in chronic inflammatory cells (Cuccurullo et al. Indian J Radiol Imaging 27:509-16, 2017) and also avidity shown previously in other IgG4-related diseases (Cheng et al. Clin Nucl Med 43:773-6, 2018).
Conjunctiva ; Eyelids ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Lacrimal Apparatus ; Muscles ; Orbit ; Orbital Diseases ; Pancreatitis ; Plasma Cells ; Positron-Emission Tomography and Computed Tomography ; Receptors, Somatostatin

Immunoglobulin G4 (IgG4)–related diseases are a spectrum of systemic inflammatory conditions of unknown etiology, which are characterized by infiltration of tissues by IgG4 plasma cells and sclerosing inflammation (Cheuk and Chan Adv Anat Pathol 17:303-32, 2010). Although this condition was initially described in relation to autoimmune pancreatitis, now it has been reported in almost every organ system of body (Zen and Nakanuma Am J Surg Pathol 34:1812-9, 2010, Masaki et al. Ann Rheuma Dis 68:1310-5, 2009). Orbital involvement by IgG4 disease can involve extraocular muscles (EOM), lacrimal glands, conjunctiva, eyelids, infraorbital nerve, orbital fat, and nasolacrimal system (McNab and McKelvie. Ophthal Plast Reconstr Surg 31:167-78, 2015, Katsura et al. Neuroradiology 54:873-82, 2012). The basis of using ⁶⁸Ga-DOTANOC PET/CT in IgG4 orbital disease is the known expression of somatostatin receptors in chronic inflammatory cells (Cuccurullo et al. Indian J Radiol Imaging 27:509-16, 2017) and also avidity shown previously in other IgG4-related diseases (Cheng et al. Clin Nucl Med 43:773-6, 2018).