CTRI/2025/04/084864 [Registered on: 16/04/2025] Trial Registered Prospectively
Last Modified On:
11/04/2026
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
This is a comparative study of Azacitidine 300 mg tablet in Adult Patients with Acute Myeloid Leukemia (Blood Cancer).
Scientific Title of Study
A Randomized, Single Oral Dose, Open Label, Two Sequence, Two Treatment, Four
Periods, 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
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
HIK-AZA-2023-01 V 4.0 dated 29 Dec 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Rakesh Patel
Designation
Head - Clinical Operations
Affiliation
Veeda Clinical research Limited
Address
Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M.,Ambawadi, Ahmadabad
Ahmadabad GUJARAT 380015 India
Phone
8308843660
Fax
Email
Rakesh.Patel@veedalifesciences.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical research Limited
Address
Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M.,Ambawadi, Ahmadabad
Ahmadabad GUJARAT 380015 India
Phone
9687306158
Fax
Email
Ravi.A1950@veedalifesciences.com
Details of Contact Person Public Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical research Limited
Address
Veeda Clinical Research Ltd., Shivalik Plaza, Near I.I.M.,Ambawadi, Ahmadabad
Ahmadabad GUJARAT 380015 India
Phone
9687306158
Fax
Email
Ravi.A1950@veedalifesciences.com
Source of Monetary or Material Support
Hikma Pharmaceuticals, Bayader Wadi Al Seer, Industrial Area, 21 Saleem Bin Hareth Street, P.O Box: 182400 Amman, 11118 Jordan
Primary Sponsor
Name
Hikma Pharmaceuticals
Address
Hikma Pharmaceuticals, Bayader Wadi Al Seer, Industrial Area, 21 Saleem Bin Hareth Street, P.O Box: 182400 Amman, 11118 Jordan
India Jordan Lebanon Saudi Arabia United Arab Emirates
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Shriram Kane
Asian Kidney Hospital and Medical Centre
213, W High Ct Rd, near Shankar Nagar, Square, Dharampeth, Nagpur, Maharashtra 440010 Nagpur MAHARASHTRA
9823012851
shriramkane@gmail.com
Dr Koustubh Shekhar
Bhartiya Vidyapith Medical college Hosptial & Research Center
Department of Medical Oncology, Bhartiya Vidyapith Medical college Hosptial & Research Center,Pune - Satara Rd, Bharati Vidyapeeth Campus, Dhankawadi, Pune, Maharashtra 411043 Pune MAHARASHTRA
9161096741
Koustubhshekar12@gmail.com
Dr Varun Bafna
Dr Bafnas Star Superspeciality Clinic and Hospital
Rukmini Nagar, E Ward, Near LIC Ground, Kolhapur-416005, Maharashtra, India Kolhapur MAHARASHTRA
9066565353
drvarunbafna6@gmail.com
Dr M Pandidurai
Hande Hospital
44, Lakshmi Talkies Rd, Shenoy Nagar, Chennai, Tamil Nadu 600030 Chennai TAMIL NADU
8248461542
pandi19@gmail.com
Dr Ramesh Upada
HCG Cancer Centre
Plot number 10, Survey no. 13P, APIIC, Health City, Arilova, Chinagadili, Vishakhapatnam-530040
Visakhapatnam ANDHRA PRADESH
9494708778
drramesh.u@hcgel.com
DrShurva Baul
Health Point Hospital
21, Prannath Pandit St, Lansdown, Paddapukur, Bhowanipore, Kolkata, West Bengal 700025 Kolkata WEST BENGAL
Dose Formulation: Tablet
Dose Strength(s):300 mg
Dosage Level(s) : 1 tablet of 300
Route of Administration: Oral
Duration of Dose: Each participant will receive study intervention (Test Product) on Day 1 and Day 3 or Day 2 and Day 4 as per the randomization schedule.
Comparator Agent
Onureg 300 mg Film Coated Tablets (300 mg Azacitidine)
Dose Formulation: Tablet
Dose Strength(s):300 mg
Dosage Level(s) : 1 tablet of 300 mg
Route of Administration: Oral
Duration of Dose: Each participant will receive Reference Product on Day 1 and Day 3 or Day 2 and Day 4 as per the randomization schedule.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Patients with documented diagnosis of AML according to the 2022 updates of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukaemia.
2. 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).
3. Patients who don’t have a known or suspected hypersensitivity to Azacitidine or any other ingredient used in the manufacturing of Azacitidine.
4. Patients who are physically able for appropriate pharmacokinetics sampling according to principal investigator evaluation.
5. Patients who have a haematological profile appropriate for receiving Azacitidine 300 mg dose for 4 consecutive days as per the principal investigator assessment.
6. Patients who understand and voluntarily sign a written informed consent document prior to any study related assessments/procedures are conducted.
7. Patient is capable of consent.
8. 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.
9. Male patients must be willing to use effective contraception during and up to 3 months after the study.
ExclusionCriteria
Details
1. Patients with history of drug or alcohol abuse
2. Female patients who are pregnant or lactating.
3. 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.
4. Patients with positive blood screen for HIV, Hepatitis B (HbsAG) or Hepatitis C (HCV) virus.
5. Patients with experience in any investigational drug in a clinical study within 6 months prior to study Day 1.
6. Patients has a difficulty fasting, consuming standard meals or history of difficulties in swallowing or any gastrointestinal disease which could affect the drug absorption.
7. 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.
8. 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.
9. 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
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.
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.
Secondary Outcome
Outcome
TimePoints
To evaluate the safety and tolerability
1. Adverse Events (AEs) [Time Frame: Up to Day 4 at discharge].
2. Change in clinical safety labs [Time Frame: Up to Day 4 at discharge].
3. Follow-up by the PI or designee will be conducted by phone call within 7 to 14 days after the last drug administration.
Target Sample Size
Total Sample Size="32" Sample Size from India="26" Final Enrollment numbers achieved (Total)= "32" Final Enrollment numbers achieved (India)="21"
Phase of Trial
N/A
Date of First Enrollment (India)
28/04/2025
Date of Study Completion (India)
28/08/2025
Date of First Enrollment (Global)
02/05/2024
Date of Study Completion (Global)
Date Missing
Estimated Duration of Trial
Years="1" Months="8" Days="0"
Recruitment Status of Trial (Global)
Completed
Recruitment Status of Trial (India)
Completed
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
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.