A multicenter, open label, balanced, randomized, single-dose, two-treatment, two period, crossover, bioequivalence study of hydroxyurea capsules 500 mg of Qilu Pharmaceutical Co., Ltd., China with that of HYDREA (hydroxyurea) capsules 500 mg of Bristol-Myers Squibb Company, Princeton, New Jersey 08543 USA in sickle cell anemia patients already on stable regimens of hydroxyurea, under fasting conditions.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 4
- 主要终点
- To assess the bioequivalence of test product (hydroxyurea capsules 500 mg) of
研究概览
简要总结
Post randomization patients will receive single dose of either test or reference productin each period [day 1 (period I) and day 8 (period II)]. There will be washout of 7days between each period.During the wash out period, patients will continue to receive locally marketedhydroxyurea.Note:ï‚· For period II, a window period of +7 days may be allowed for any social reasonor any other unavoidable circumstances etc. and +14 days may be allowed for AEmanagement.ï‚· Dosing activity will be done under sodium vapor lamp in both periods.
Patients will be administered drug in sitting position posture. Patients will be advisedto remain in sitting or ambulatory position for the first 04 hours after IMPadministration. Patients will be advised to avoid any strenuous activity throughoutstudy period. Thereafter, the patients will be allowed to engage only in normalactivities while avoiding severe physical exertion.
Patients will be housed in clinical facility at least 12 hrs prior to scheduled dosing ineach period. Patients will continue to remain in the facility for at least 24 hours afterdosing in each period.The patients will have to stay at least 2 consecutive nights in clinical facility in eachperiod.
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 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patients of either gender (Male or Female) ≥18 years of age with confirmed diagnosis of sickle cell anemia.
- •2.Patients that are already on a stable dosing regimen of hydroxyurea (500 mg taken once daily) for at least 24 weeks prior to screening in the study.
- •3.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.
- •4.Adequate Hematopoietic, Renal and Hepatic function defined as the following: Body systemParameters Bone marrow functionANC  1500/mm3 Platelet count  100,000/mm3 Haemoglobin > 9.0 g/dl Hepatic functionALT/AST ≤ 2.5 × ULN Total Bilirubin ≤ 1.5 ×ULN Renal functionCreatinine clearance ≥ 60 ml/min (calculated based on Cockcroft-Gault formula) 5.Able to comply with study requirement in opinion of Principal Investigator.
- •6.Females of childbearing potential must have a negative beta-HCG pregnancy test at screening and negative urine pregnancy test at the time of check-in.
- •7.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] during study and for atleast 6 months after the last dose of study drug.
- •Cessation of birth control after this point should be discussed with a responsible physician.
- •8.Males of reproductive potential must agree to use effective contraception [including use of barrier methods (male condom, spermicide), behavioral methods (abstinence) or vasectomy] or the female partners of these patients must agree to use an effective method of avoiding pregnancy as defined in the inclusion criteria no.
- •7, during the study and for atleast 1 year after the last dose of study drug.
- •Cessation of birth control after this point should be discussed with a responsible physician It is investigator responsibility to ensure that above points regarding an effective method of avoiding pregnancy are discussed with patient or legally acceptable representative LAR in detail and patient agreed for this and it is documented in source document.
排除标准
- •1.History of hypersensitivity to hydroxyurea or any other component of its formulation as judged by the investigator.
- •2.History of a myeloproliferative disease, diffuse pulmonary infiltrates or pulmonary fibrosis.
- •3.History of therapy with central nervous system inhibitor or antitumor agents (e.g. 5-fluorouracil) within 28 days before the first administration of investigational product.
- •4.History of therapy with interferon or antiretroviral agents (e.g. didanosine, stavudine and indinavir) within 28 days before the first administration of investigational product.
- •5.Patients with leukemia of any type.
- •6.Uncontrolled systemic infection.
- •7.Cardiac diseases including congestive heart failure, atrial or ventricular arrhythmia.
- •8.History of drug/alcohol addiction.
- •9.Pregnant or lactating females.
- •10.Patients found to be positive for HIV, Hepatitis B or C, VDRL at screening.
- •11.Patients requiring dosing with any of the live vaccines.
- •12.Patients suffering from gout.
- •13.Patients with skin cancer or other secondary malignancies.
- •14.Patients with cutaneous vasculitic toxicities, including vasculitic ulcerations, gangrene, etc.
- •15.Patients with history of diagnosis of macrocytosis or pernicious anemia.
- •16.Patients with a history of tumor lysis syndrome, disorientation, hallucinations, convulsions etc.
- •following treatment with hydroxyurea.
- •19.Inadequate venous access for PK sampling as judged by investigator.
- •20.Requirement of any planned procedure or hospitalization for pre-existing conditions during the study period.
- •21.Patients found positive on urine scan for drugs of abuse and/or breath / other relevant test for alcohol consumption at screening and baseline.
- •22.The receipt of an investigational medicinal product or participation in other drug research study within a period of 30 days (or 5 half-lives, whichever is longer) prior to the first dose of investigational medicinal product for the current study.
- •Note: Elimination half-life of the study drug should be taken in to consideration for inclusion of the patient in the study.
- •23.Patients with any significant history of non-compliance or inability to reliably grant informed consent.
- •25.Patients in whom oral administration of IMP is not possible.
结局指标
主要结局
To assess the bioequivalence of test product (hydroxyurea capsules 500 mg) of
时间窗: A total of 24 blood samples for PK assessment in period I(visit 2) & period II (visit 3),The pre-dose blood sample of 4 mL will be collected within one hour prior to the dosing.
Qilu Pharmaceutical Co., Ltd., China with that of reference product HYDREA
时间窗: A total of 24 blood samples for PK assessment in period I(visit 2) & period II (visit 3),The pre-dose blood sample of 4 mL will be collected within one hour prior to the dosing.
(hydroxyurea) capsules 500 mg of Bristol-Myers Squibb Company, Princeton,
时间窗: A total of 24 blood samples for PK assessment in period I(visit 2) & period II (visit 3),The pre-dose blood sample of 4 mL will be collected within one hour prior to the dosing.
New Jersey 08543 USA in sickle cell anemia patients already receiving a stable
时间窗: A total of 24 blood samples for PK assessment in period I(visit 2) & period II (visit 3),The pre-dose blood sample of 4 mL will be collected within one hour prior to the dosing.
dosing regimen of hydroxyurea under fasting conditions.
时间窗: A total of 24 blood samples for PK assessment in period I(visit 2) & period II (visit 3),The pre-dose blood sample of 4 mL will be collected within one hour prior to the dosing.
次要结局
- To monitor the safety and tolerability profile of the study formulations in sickle(cell anemia patients.)