A multicenter, open label, balanced, randomized, two-treatment, three-period, three-sequence, partial replicate, single dose, cross-over bioequivalence study of Azacitidine film-coated tablets 300 mg and ONUREGTM (Azacitidine) film-coated tablets 300 mg in adult patients with acute myeloid leukemia (AML) under fasting condition.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 18
- 主要终点
- To assess the pharmacokinetics & establish bioequivalence of the sponsor’s Test Product (Azacitidine 300 mg film-coated tablet) relative to that of Reference Product ONUREGTM (Azacitidine) 300 mg film-coated tablet in adult acute myeloid leukemia patients who have achieved complete remission or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy.
研究概览
简要总结
This is partial replicate (reference replicate) bioequivalence study between test and reference product in patients diagnosed with acute myeloid leukaemia (AML) (from multiple sites in India) who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy with or without consolidation therapy; and who are not eligible for hematopoietic stem cell transplantation (HSCT) and hence, are eligible to receive Azacitidine 300 mg film-coThis is partial replicate (reference replicate) bioequivalence study between test and reference product in patients diagnosed with acute myeloid leukaemia (AML) (from multiple sites in India) who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy with or without consolidation therapy; and who are not eligible for hematopoietic stem cell transplantation (HSCT) and hence, are eligible to receive Azacitidine 300 mg film-coated tablet once daily, will be enrolled after getting written informed consent.
As per the summary of product characteristics, Azacitidine 300 mg film-coated tablet is to be administered orally once daily on Days 1 through 14 of each 28-day cycle. The study will be conducted on day 1, day 2 and day 3 of treatment cycle (i.e. at the beginning of the treatment cycle) that the patient is scheduled to receive.
In the study, treatments will be randomly allocated to patients in accordance with a randomization schedule prepared using statistical techniques. Reference-scaling will be done where-in patients will receive reference drug in any of the two periods and test product in one period in a crossover manner. Patients will be randomly allocated to the treatment sequence- TRR or RTR or RRT.
Total duration of study will be 14 days consists of a screening period of 10 days prior to first study drug administration followed by
ü Check in on Day 0 ( 11 hours prior to drug administration of Day 1)
ü Study drug administration on Day 1 (period-I), Day 2 (period-II) and Day 3 (period-III) considering the washout period of 24 hours between each dosing.
ü Hospitalization on Day 0 (Check-in) to Day 3 (Check-out) in the study. For patient convenience, check-out may be done on Day-4 at the discretion of Investigator.
ü PK Sampling onDay 1 to Day 3 of the study.
ü End of the study after last PK sample collection on Day 3.
Patients will be provided Azacitidine film coated tablet 300mg as compassionate medication for the remainder of the cycle (day 4 to day 14) as per the discretion of the investigator.
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.Male or non-pregnant, non-lactating female patient ≥18 years of age.
- •2.Able to give written informed consent for participation in the trial.
- •3.Patients with documented diagnosis of Acute myeloid leukemia (AML) who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy with or without consolidation therapy.
- •4.Patients that are to be initiated on consolidation therapy with Azacitidine 300 mg tablet or patients who are already on a stable dose of Azacitidine 300 mg tablet (for these patients a washout of 14 days of their ongoing Azacitidine 300 mg tablet must be ensured prior to randomization in the study).
- •5.Patient having an estimated survival of ≥3 months.
- •6.Adequate organ and bone marrow function based upon the following laboratory criteria at the time of eligibility assessment: Body systemParameters Bone marrow functiona)Hemoglobin ≥8.0 g/dL b)Absolute neutrophil count ≥1000/uL c)Platelet count ≥75,000/uL Renal functionCreatinine Clearance ≥ 30 mL/min (calculated based on Cockcroft-Gault formula) Hepatic functionTotal Bilirubin ï‚£ 1.5 times ULN SGOT (AST) ï‚£ 2.5 times ULN SGPT (ALT) ï‚£ 2.5 times ULN 7.Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •8.12-lead ECG with no clinically significant findings at screening.
- •As determined by the Investigator.
- •9.Women of child bearing potential, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months, must have negative pregnancy test at screening visit and before randomization and must agree to use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during the study and up to 6 months after the last dose of study drug.
- •Cessation of birth control after this point should be discussed with a responsible physician.
- •10.In case of Male patients: The patient and his partner must agree to use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during the study and up to 3 months after the last dose of study drug.
排除标准
- •1.History of known hypersensitivity to azacitidine or its components which, in the opinion of the Investigator, would compromise the safety of the patient or the results of the study.
- •2.Patients found positive for HIV, Hepatitis B surface antigen or Hepatitis C antibody at screening.
- •3.Have ongoing clinically significant adverse event due to prior treatments administered, as determined by the investigator.
- •4.History of inflammatory bowel disease e.g. Crohn disease, ulcerative colitis , celiac disease, prior gastrectomy, gastric bypass, upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption of the study drug and/or predispose the patient to an increased risk of gastrointestinal toxicity.
- •5.Patients treated with proton pump inhibitors (PPIs) like Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole and Rabeprazole within 4 weeks prior to start of IMP or require as concomitant medication.
- •6.In the opinion of the Investigator, the patient will not be compliant with the requirements of the study procedures.
- •7.Participation in another drug research study within 90 Days (or 5 half-lives, whichever is longer) prior to receiving the first dose of investigational medicinal product for the current study.
- •8.History of difficulty in accessibility of veins 9.Patient positive on Breath alcohol analyzer test at the time of baseline visit (Check in Day 0).
- •10.Positive for drugs of abuse prior to receiving the first dose of investigational medicinal product in the study.
- •Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drug, or which may jeopardize the patient in case of participation in the study.
- •12.Patients with psychiatric illness/social situations that would limit compliance with study requirements.
- •13.Patients with any uncontrolled medical condition e.g. cardiovascular disease, hypertension, diabetes mellitus etc.
- •or active infection, etc or any abnormal laboratory findings, which, in the Investigator opinion, would contraindicate, or interfere with absorption of the study drug or jeopardize the safety of the patient.
- •14.Patients with impaired ability to swallow oral medication.
- •15.Patients with uncontrolled systemic fungal, bacterial, or viral infection patients.
结局指标
主要结局
To assess the pharmacokinetics & establish bioequivalence of the sponsor’s Test Product (Azacitidine 300 mg film-coated tablet) relative to that of Reference Product ONUREGTM (Azacitidine) 300 mg film-coated tablet in adult acute myeloid leukemia patients who have achieved complete remission or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy.
时间窗: A total of 48 blood samples, each of 03 mL, will be collected from each patient for PK assessment during the study. | On Day 1 (Period I), Day 2 (Period II) & Day 3 (Period III): | The pre-dose PK blood sample of 03 mL (0.00 hr) will be collected within 5 min prior to the dosing. | Post dose PK blood samples of 03 mL will be drawn at 0.167, 0.333, 0.50, 0.75, 1.0, 1.25, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0,4.5, 5.0 & 6.0 hours following drug administration in each period)
次要结局
- To monitor the adverse events & to ensure the safety of the patients.(Day 1, Day 2, day 3, Day 4)