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) Tablet 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.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 12
- 主要终点
- To assess biequivalence of intervention product compared to comparator product at steady state pharmacokinetics under fed conditions
研究概览
简要总结
Imatinib mesylate a selective inhibitor of BCR-ABL kinase activity, has demonstrated significant clinical efficacy in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST) producing durable responses and prolonged survival such that it has become the standard of care for these diseases. Imatinib has favorable pharmacokinetic (PK) characteristics, including rapid and complete oral bioavailability (nearly 98%) and a proportional dose-exposure relationship. Its terminal half-life is approximately 20 hours, allowing for once daily dosing.
Amneal Pharmaceuticals, LLC (Amneal) has developed generic version of imatinib mesylate tablets EQ 400 mg base. The present study aims to evaluate bioequivalence of Amneal’s test formulation against corresponding reference product GLEEVEC® (imatinib mesylate) tablet 400 mg distributed by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936 in adult patients, who are diagnosed to have CML or GIST and are presently being treated with imatinib oral tablets.
Primary objective: To characterize pharmacokinetic profile of test product – Imatinib Mesylate tablet EQ 400 mg base of Amneal Pharmaceuticals, LLC, compared to that of the corresponding reference product – GLEEVEC® (imatinib mesylate) tablet 400 mg distributed by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936 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.
Secondary Objective: To monitor the safety and tolerability of a multiple doses of Imatinib Mesylate Tablets EQ 400 mg base in adult patients, who are diagnosed to have CML or GIST and are presently receiving stable dose of Imatinib Mesylate tablets 400 mg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 55.00 Year(s)（—）
- 性别
- All
入选标准
- •Diagnosed case of Philadelphia chromosome positive (Ph+) CML or GIST and presently being treated with imatinib 400 mg tablets.
- •Willing to give written informed consent for participation in the trial 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 been hysterectomized) must have negative serum pregnancy test at the screening, negative urine pregnancy test on check in to housing and must agree to use effective contraception (barrier or hormonal) for the study period.
排除标准
- •The Patients with any of the following criteria should be excluded.
- •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, • Absolute neutrophils count less than 1000/ mm3 • Platelet Count less than 50,000/mm3 • SGOT and/or SGPT greater than 5 times upper limit of normal (ULN) • Serum total Bilirubin greater than 3 times ULN • Serum TSH greater than 10 microIU/mL • Serum Uric Acid greater than 12 mg/dL • Reactive for HIV antibody, HBsAg or HCV antibody
- •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 within 14 days • Inhibitors of CYP3A4 activity within 14 days.
- •â€¢ Investigational product/ device within last one month
- •Alcohol or any drug dependence within past one year.
结局指标
主要结局
To assess biequivalence of intervention product compared to comparator product at steady state pharmacokinetics under fed conditions
时间窗: Blood sampling will be done from predose to untill 24 hours after the dosing on day 7 and day 14 of the study
次要结局
- Safety and tolerability of intervention product compared to comparator product by adverse events(Throughout the study from dosing till follow up on day 22)