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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chronic Myeloid Leukemia, Gastrointestinal Stromal Tumor

Intervention / Treatment
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* Drug: Imatinib Mesylate Tablets, 400 mg
* Drug: Imatinib Mesylate Tablets, 400 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib Mesylate Tablets, 400 mg<br>Imatinib Mesylate Tablets, 400 mg. Once daily for 14 days. | Drug: Imatinib Mesylate Tablets, 400 mg<br>* Brown, oval, scored, film coated, beveled edge tablet. Debossed with AN on scored side and 795 on the other side.<br>|
| Active Comparator: Gleevec Tablets, 400 mg<br>Imatinib Mesylate Tablets, 400 mg. Once daily for 14 days. | Drug: Imatinib Mesylate Tablets, 400 mg<br>* 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.<br>* Other names: Gleevec;|

What is the study measuring?
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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 |