A multicentre, randomized, open label, steady state, two treatment, two period, two-way crossover, bioequivalence study under fed conditions comparing Imatinib Mesylate Tablets 400 mg of CSPC Pharmaceutical, China to the reference drug Gleevec® (Imatinib Mesylate) Tablets 400 mg of Novartis Pharma Stein AG,for Novartis Pharmaceuticals Corporation New Jersey in patients of Philadelphia chromosome positive Chronic Myeloid Leukaemia (CML), stabilized on Imatinib Mesylate 400 mg.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 26
- 试验地点
- 4
- 主要终点
- To characterize and compare the pharmacokinetic profile of the sponsor’s test
研究概览
简要总结
Imatinib mesylate (Imatinib) is a selective inhibitor of the protein tyrosine kinase associated with bcr-abl and specifically inhibits proliferation of Ph expressing cells. To prevent healthy volunteers from adverse events and as per Guidance on the conduct of bioequivalence study with Imatinib Mesylate4, this study is proposed to be carried out on patients of Chronic Myeloid Leukaemia (CML) in chronic Phase who are stabilized with Imatinib Mesylate 400 mg tablets for atleast 30 days and having documented evidence of Philadelphia chromosome positive. The dosing and sampling regime is proposed to be built into the recommended treatment of such patients. The recommended dosing regime is Imatinib 400 mg daily for adult patients of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.
In this study, Imatinib Mesylate 400 mg (Test and Reference) will be administered to patients at an interval of 24 hr for 14 days. Day 1 to day 7 will be considered period I and day 8 to day 14 will be considered as period II.
Following oral administration, the elimination half-life of Imatinib and its major active metabolite, the N-demethyl derivative, are approximately 18 and 40 hours, respectively. Therefore, this steady state multiple dose study will be performed in patients of Philadelphia chromosome positive Chronic Myeloid Leukaemia (CML), who are stabilized with Imatinib mesylate 400 mg for atleast 30 days.
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 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients able to give informed consent for participation in the trial.
- •Male or female patients must be 18 to 65 years of age (both inclusive) at the screening visit.
- •Patient must be on stable dose of Imatinib Mesylate 400 mg for at least 30 days prior to dosing.
- •Patients of Chronic Myeloid Leukemia in chronic phase with documented evidence of Philadelphia chromosome positive (Ph+ CML).
- •Patient must have an ECOG performance status of 0-
- •Patient must have an adequate bone marrow, renal and hepatic function.
- •Patient should be able to comply with study procedures in the opinion of the investigator.
- •In case of female patient the serum pregnancy test at screening visit and urine pregnancy test at day 1 (before dosing) must be negative.
- •Sexually active women, unless surgically sterile (at least 6 months prior to Study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug administration] sexual partner) for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
- •Cessation of birth control after this point should be discussed with a responsible physician.
- •In case of Male patients: Either partner or patient must use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
- •It is investigator’s responsibility to ensure that above points regarding an effective method of avoiding pregnancy are discussed with patient in detail and patient agreed for this and it is documented in source document.
- •The investigator should ensure that the patient is using an effective method of avoiding pregnancy as per protocol.
排除标准
- •Known hyper sensitivity to Imatinib or any of its excipients or related group of drugs.
- •Patients with known human immunodeficiency virus (HIV) infection.
- •A positive hepatitis screen including hepatitis B surface antigen, HCV and HAV antibodies.
- •Patients of Ph+ CML in Accelerated Phase (AP) or Blast Crisis (BP).
- •Have previously undergone hematopoietic stem cell transplantation.
- •Patient is on drugs known to be inducer or inhibitor of CYP3A4 family.
- •Patient who have undergone Thyroidectomy.
- •Use of any recreational drugs or history of drug addiction.
- •Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product for the current study.
- •Any other condition or abnormal baseline findings that, in the investigator’s judgement, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
- •The receipt of an investigational medicinal product within a period of 30 days prior to the first dose of investigational medicinal Product for the current study.
- •Patient with a history of difficulty in donating blood or difficulty in accessibility of veins.
- •Patient with history of Hepatotoxicity.
结局指标
主要结局
To characterize and compare the pharmacokinetic profile of the sponsor’s test
时间窗: Day 1 to Day 14
formulation (Imatinib Mesylate Tablets 400 mg) relative to that of reference
时间窗: Day 1 to Day 14
under fed conditions.
时间窗: Day 1 to Day 14
formulation (Gleevec® (Imatinib Mesylate) Tablets 400mg) in adult philadelphia
时间窗: Day 1 to Day 14
chromosome positive chronic myeloid leukemia patients stabilized with Imatinib
时间窗: Day 1 to Day 14
mesylate 400 mg and to assess the bioequivalence after multiple dose administration
时间窗: Day 1 to Day 14
次要结局
- To monitor the safety of the patients exposed to the Investigational Medicinal Product.(Day 1 to Day 14)