A Clinical Trial to Compare the Pharmacokinetics of Imatinib Mesylate Tablet 400mg (1 Tablet) and Glivec Film-coated Tablet 100mg (4 Tablets)(Phase I)

A Randomized, Open-label, Single-dose, Crossover Clinical Trial to Compare the Pharmacokinetics of Imatinib Mesylate Tablet 400 mg (1 Tablet) and Glivec Film-coated Tablet 100 mg (4 Tablets) After Oral Administration in Healthy Male Subjects (Phase I)

1. Investigational Product

   1. Imatinib mesylate tablet 400 mg
   2. Glivec film-coated tablet 100 mg (Comparator)

2. Expected target disease

   1. chronic myeloid leukemia
   2. Gastrointestinal stromal tumors

3. Study design : Randomized, open-label, single dose, two-period, two-way, crossover study

   1. 36 healthy subjects, 2 groups (18 subjects/group)
   2. 2 Period (either 1-a(1 tablet) or 1-b(4 tablet))
   3. wash-out period : 14 days

4. Evaluation on pharmacokinetics(PKs) and safety

   1. PKs : Cmax, AUClast, Tmax, AUCinf, t1/2
   2. safety : adverse events, physical examination, vital sign, ECG, Laboratory test

5. Statistical method

   1. Demography Characteristics
   2. Pharmacokinetic parameters
   3. Safety data

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukemia; Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: Imatinib mesylate tablet 400 mg, 1 Tablet; Drug: Glivec film-coated tablet 100 mg, 4 Tablets

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Kyungpook National University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy male volunteers between the ages of 20 to 50 years old
• weight more than 55kg and within the range of ±20% of ideal body weight (IBW)
• having neither congenital/chronic diseases nor pathological symptoms/findings as results of medical examination
• doctor determines to be suitable as subjects within 3 weeks ago before administration

Exclusion Criteria:

• Hypersensitivity(or history of hypersensitivity) to medicines including imatinib mesylate
• Active Liver Diseases or exceed 1.5 times the normal range of AST, ALT, total bilirubin
• Creatinine clearance < 80 mL/min
• Gastrointestinal diseases or surgeries that affect absorption of drug
• Excessive drinking(exceed 21units/week)
• Smoking over 10 cigarettes per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group 1 (RT); Period 1: Glivec film-coated tablet 100 mg, 4 tablets (Active comparator); Period 2: Imatinib mesylate tablet 400 mg, 1 tablet (experimental)	Drug: Imatinib mesylate tablet 400 mg, 1 Tablet; Drug: Glivec film-coated tablet 100 mg, 4 Tablets
Other: Group 2 (TR); Period 1: Imatinib mesylate tablet 400 mg, 1 tablet (experimental); Period 2: Glivec film-coated tablet 100 mg, 4 tablets (Active comparator)	Drug: Imatinib mesylate tablet 400 mg, 1 Tablet; Drug: Glivec film-coated tablet 100 mg, 4 Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration in plasma (Cmax) of Imatinib mesylate	Pre-dose(0h) AND 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 h post-dose
Area under the plasma concentration-time curve from zero time until the last measurable concentration (AUClast) of Imatinib mesylate	Pre-dose(0h) AND 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 h post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Cmax (Tmax) of Imatinib mesylate	Pre-dose(0h) AND 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 h post-dose
Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of Imatinib mesylate	Pre-dose(0h) AND 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 h post-dose
Terminal Elimination Half-life (t1/2) of Imatinib mesylate	Pre-dose(0h) AND 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 h post-dose

Collaborators and Investigators

• Sponsor: Dong-A ST Co., Ltd.

Publications and helpful links

General Publications

• Parrillo-Campiglia S, Ercoli MC, Umpierrez O, Rodriguez P, Marquez S, Guarneri C, Estevez-Parrillo FT, Laurenz M, Estevez-Carrizo FE. Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers. Clin Ther. 2009 Oct;31(10):2224-32. doi: 10.1016/j.clinthera.2009.10.009.
• Nikolova Z, Peng B, Hubert M, Sieberling M, Keller U, Ho YY, Schran H, Capdeville R. Bioequivalence, safety, and tolerability of imatinib tablets compared with capsules. Cancer Chemother Pharmacol. 2004 May;53(5):433-8. doi: 10.1007/s00280-003-0756-z.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: December 14, 2012
• First Submitted That Met QC Criteria: December 14, 2012
• First Posted (Estimate): December 18, 2012

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 29, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: CML; GIST
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Myeloproliferative Disorders; Leukemia; Neoplasms, Connective Tissue; Leukemia, Myeloid; Gastrointestinal Stromal Tumors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: Imatinib_CML_I