Comparative Bioequivalence Study in Adult Patients Suffering From Chronic Myeloid Leukemia & Gastrointestinal Stromal Tumor Under Fed Conditions

A Randomized, Open Label, Two-Treatment, Multiple Dose, Steady State, Two-period, Cross-over, Multi-Centre Comparative Bioequivalence Study of Imatinib Mesylate Tablet 400 mg of Amneal Pharmaceuticals, USA With GLEEVEC® (Imatinib Mesylate) Tablets 400 mg Distributed by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936 in Adult Patients Suffering From Chronic Myeloid Leukemia & Gastrointestinal Stromal Tumor Under Fed Conditions

To characterize pharmacokinetic profile of test product compared to that of the corresponding reference product in adult patients, who are diagnosed to have Chronic Myeloid Leukemia & Gastrointestinal Stromal Tumor under Fed Conditions.

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukemia; Gastrointestinal Stromal Tumor
• Intervention / Treatment: Drug: Imatinib Mesylate Tablets, 400 mg; Drug: Imatinib Mesylate Tablets, 400 mg

Detailed Description

To characterize pharmacokinetic profile of Imatinib Mesylate tablets EQ 400 mg base of Amneal Pharmaceuticals LLC, compared to that of the reference product - GLEEVEC® (imatinib mesylate) tablets 400 mg in adult patients, who are diagnosed to have CML or GIST and are presently receiving stable dose of imatinib mesylate tablets 400 mg, and assess their bioequivalence.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Gujurat
    • Vadodara, Gujurat, India, 391760
      • Kailash Cancer Hospital & Research Centre
  • Karnataka
    • Bangalore, Karnataka, India, 560076
      • Srinivasam Cancer Care Hospitals India Pvt.
    • Bengaluru, Karnataka, India, 560096
      • Karnataka Caner Hospital
  • Maharashtra
    • Pune, Maharashtra, India, 411044
      • Lokmaya Hospital
  • Tamil Nadu
    • Tiruchirappalli, Tamil Nadu, India, 620 008
      • Dr. G Viswanathan Speciality Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 55 years (both inclusive) and either sex
• Diagnosed case of Philadelphia chromosome positive (Ph+) CML patients in chronic phase or GIST and presently being treated with imatinib 400 mg tablets.
• Willing to give written informed consent for participation in the study as well as willing and able to comply with study visit schedule and other protocol requirements.
• Female patients of child bearing potential (except for those who have completed one year since menopause or have gone through hysterectomy or bilateral tubal ligation) must have negative serum pregnancy test at the screening, negative urine pregnancy test on check in to housing, must be non-lactating at screening and must agree to use effective contraception (barrier or hormonal) for the study period.

Exclusion Criteria:

• History of hypersensitivity to imatinib mesylate or to any of the excipients as judged by investigator.
• Patient of CML receiving treatment in Myeloid Blast Crisis or Accelerated Phase
• Abnormal laboratory results as below:
• History of a heart failure, renal insufficiency, hypereosinophilic syndrome (HES), myelodysplastic syndrome (MDS)/ myeloproliferative disease (MPD) or acute systemic mastocytosis (ASM).
• History of therapy with any of the following as per timelines before randomization: inducers of CYP3A4 activity and inhibitors of CYP3A4 activity, within 14 days, investigational product/device within last one month
• Alcohol or any drug dependence within past one year.
• Blood donation/loss exceeding 200 ml within last 60 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Imatinib Mesylate Tablets, 400 mg; Imatinib Mesylate Tablets, 400 mg. Once daily for 14 days.	Drug: Imatinib Mesylate Tablets, 400 mg; Brown, oval, scored, film coated, beveled edge tablet. Debossed with AN on scored side and 795 on the other side.; Drug: Imatinib Mesylate Tablets, 400 mg; Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with "400" on one side with score on the other side, and "SL" on each side of the score.; Other Names: Gleevec
ACTIVE_COMPARATOR: Gleevec Tablets, 400 mg; Imatinib Mesylate Tablets, 400 mg. Once daily for 14 days.	Drug: Imatinib Mesylate Tablets, 400 mg; Brown, oval, scored, film coated, beveled edge tablet. Debossed with AN on scored side and 795 on the other side.; Drug: Imatinib Mesylate Tablets, 400 mg; Very dark yellow to brownish orange, film-coated tablets, ovaloid, biconvex with bevelled edges, debossed with "400" on one side with score on the other side, and "SL" on each side of the score.; Other Names: Gleevec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Peak maximum concentration over dosing interval in the steady state	Days 5, 6, 7, 12, 13, 14 and 15
AUC0-tau	The area under the blood concentration curve versus time, calculated by the trapezoid method, from zero time to the dose interval (tau) in the steady state	Days 5, 6, 7, 12, 13, 14 and 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	The time to reach such peak over dosing interval in the steady state	Days 5, 6, 7, 12, 13, 14 and 15
Cmin	Minimum concentration established at each dose interval end of the steady state	Days 5, 6, 7, 12, 13, 14 and 15
Cavg	Average concentration in the steady state (= AUC0-tau / tau)	Days 5, 6, 7, 12, 13, 14 and 15
Swing	Swing in steady state pharmacokinetics, calculated as (CmaxSS-CminSS)/ CminSS	Days 5, 6, 7, 12, 13, 14 and 15
Fluctuation Rate	Degree of fluctuation in the steady state pharmacokinetics, calculated as (Cmax-Cmin)/CavSS	Days 5, 6, 7, 12, 13, 14 and 15

Collaborators and Investigators

• Sponsor: Amneal Pharmaceuticals, LLC
• Collaborators: Accutest Research Laboratories (I) Pvt. Ltd.
• Investigators: Principal Investigator: Ashutosh Jani, MD, Accutest Research Laboratories (I) Pvt. Ltd.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: April 1, 2014
• First Submitted That Met QC Criteria: April 1, 2014
• First Posted (ESTIMATE): April 3, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): June 27, 2014
• Last Update Submitted That Met QC Criteria: June 25, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• 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; Neoplasms, Connective Tissue; Leukemia; 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: ARL/CT/13/001