A Randomized, Single Oral Dose, Open Label, Two Sequence, Two Treatment, FourPeriods, Full Replicate Crossover Study to Determine the Bioequivalence of Azacitidine 300 mg Film - coated Tablets Versus Onureg® 300 mg Film-Coated Tablets for Adult Patients with Acute Myeloid Leukaemia (AML) under Fasting Conditions
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 32
- 试验地点
- 10
- 主要终点
- To investigate the bioequivalence of the Test Product (Azacitidine 300 mg Film coated tablets (300 mg Azacitidine) manufactured for Hikma Pharmaceuticals (MAH)) relative to Reference Product (Onureg 300 mg Film Coated Tablets (300 mg Azacitidine) manufactured by Celgene Corporation after a single oral dose administration in adult patients with AML under fasting conditions.
研究概览
简要总结
This is randomized, two treatment, four period, full replicate, crossover, bioequivalence study between test and reference product in patients diagnosed with acute myeloid leukaemia (AML) who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy will be enrolled after getting written informed consent.
All eligible patients will be randomly assigned to receive a single dose of 300 mg Azacitidine of either test product (two doses, one dose in each period) or the reference product (two doses, one dose in each period) with 240 ml of water after atleast 10 hours of overnight fasting on each night using IWRS . Patients will be randomized into two treatment sequence groups, sequence 1 (TRTR) and sequence 2 (RTRT), where T represents the test product and R represents the reference product).
The study consists of a screening period of 14 days and 4 treatment periods of 1 day each, of the same treatment cycle (Period I [Day 1], Period II [Day 2], Period III [Day 3] and Period IV [Day 4]).
Total duration of study will be 32 days (Approximately) for each patient consists of a screening period of 14 days prior to first study drug administration wherein:
Check in on Day -1
Study drug administration on Day 1 (period-I), Day 2 (period-II), Day 3 (period-III) and Day 4 (Period-IV).
Discharge on Day 4 after completion of study activities.
Follow-up by the PI or designee by phone call within 7 to 14 days after the last Azacitidine drug administration.
Total 56 PK Samples will be collected on Day 1 to Day 4 of the study.
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
- •Patients with documented diagnosis of AML according to the 2022 updates of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukaemia.
- •Patients with AML who achieved first complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and are not able to complete intensive curative therapy.
- •The definitions of response criteria for CR or CRi are primarily those defined by the 2022 report from the European Leukemia Net (ELN) on AML as below: CR defined as bone marrow blasts less than 5%; absence of circulating blasts; absence of extramedullary disease; ANC equal to or more than 1.0 × 10^9/L (1,000/µL); platelet count equal to or more than 100 × 10^9/L (100 000/µL).
- •CRi defined as all CR criteria, except for residual, neutropenia less than 1.0 × 10^9/L (1,000/µL) or thrombocytopenia less than 100 × 10^9/L (100 000/µL).
- •Patients who don’t have a known or suspected hypersensitivity to Azacitidine or any other ingredient used in the manufacturing of Azacitidine.
- •Patients who are physically able for appropriate pharmacokinetics sampling according to principal investigator evaluation.
- •Patients who have a haematological profile appropriate for receiving Azacitidine 300 mg dose for 4 consecutive days as per the principal investigator assessment.
- •Patients who understand and voluntarily sign a written informed consent document prior to any study related assessments/procedures are conducted.
- •Patient is capable of consent.
- •Females of childbearing potential may participate, providing the subject meets the following conditions: Negative serum pregnancy test at screening, and willing to use effective contraception during and up to 6 months after study.
- •Male patients must be willing to use effective contraception during and up to 3 months after the study.
排除标准
- •Patients with history of drug or alcohol abuse
- •Female patients who are pregnant or lactating.
- •Patients with medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the investigator, might interfere with subject safety, compliance or evaluation of the condition of the study.
- •Patients with positive blood screen for HIV, Hepatitis B (HbsAG) or Hepatitis C (HCV) virus.
- •Patients with experience in any investigational drug in a clinical study within 6 months prior to study Day
- •Patients has a difficulty fasting, consuming standard meals or history of difficulties in swallowing or any gastrointestinal disease which could affect the drug absorption.
- •Patients does not agree to not be engaged in strenuous exercise at least one day prior to study drug administration until donating the last sample of the study.
- •Patients does not agree to not consuming any beverages or food containing grapefruit for at least two weeks prior to first study drug administration until donating the last sample of the study.
- •Patients does not agree to not consuming any beverages or food containing methyl-xanthines e.g., caffeine (coffee, tea, cola, energy drinks, chocolate etc.) and alcohol containing beverages at least 48 hours prior to first study drug administration until donating the last sample of the study.
结局指标
主要结局
To investigate the bioequivalence of the Test Product (Azacitidine 300 mg Film coated tablets (300 mg Azacitidine) manufactured for Hikma Pharmaceuticals (MAH)) relative to Reference Product (Onureg 300 mg Film Coated Tablets (300 mg Azacitidine) manufactured by Celgene Corporation after a single oral dose administration in adult patients with AML under fasting conditions.
时间窗: On each period 14 blood samples will be collected, 1 predose sample at 0.00 hr and 13 post dose sample at 0.167 (10 mins), 0.333 (20 mins), 0.50 (30 mins), 0.75 (45 mins) ,1.00, 1.25, 1.50, 1.75, 2.00 ,2.50, 3.00, 4.00 and 5.00 hours.
次要结局
- To evaluate the safety and tolerability(1. Adverse Events (AEs) [Time Frame: Up to Day 4 at discharge].)