| CTRI Number |
CTRI/2025/04/084864 [Registered on: 16/04/2025] Trial Registered Prospectively |
| Last Modified On: |
11/04/2025 |
| 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 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Veeda ClinicalResearch Ltd |
Veeda Clinical Research Ltd., Shivalik Plaza,Near I.I.M., Ambawadi Ahmedabad – 380015,India |
|
|
Countries of Recruitment
|
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 |
9062015351
dr.shuvra.n.baul@gmail.com |
| Dr Sandeep Nemani |
Horizon Multispeciality Hospital |
S. No. 90/2B/1A/2A/1, Plot No. 1+3, Dhamani Road, Sangli- 416410
Sangli
MAHARASHTRA |
9786698133
dr.nemani@gmail.com |
| Dr Manoj Toshniwal |
Ishwar Institute of Health Care |
Room No. 107, First floor,Ishwar Heights, Plot No 07, Gut No 06 by 1, Beside Punjabi Bhawan, padegoan, Aurangabad 431002
Aurangabad
MAHARASHTRA |
9225300842
drmanojtoshniwal.iicr@gmail.com |
| Dr Smitha C Saldanha |
Nano Hospitals |
#79, Sir M Visveswaraya Rd, Near Arekere Saibaba Temple, Off Bannerghata Road, Bengaluru, 560076
Bangalore
KARNATAKA |
9480852106
scsclinicals@gmail.com |
| Dr Amee Patel |
PP Maniya Hospital PVT LTD |
12, Mamata Park Society-1, Opposite Dharuka College, Varachha Main road, Kapodra, Surat, Gujarat 395006
Surat
GUJARAT |
9979456297
doctoramipatel@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 10 |
| Name of Committee |
Approval Status |
| EC-Horizon Multispeciality Hospital |
Submittted/Under Review |
| Ethics Committee of Ishwar Institue of HealthCare |
Submittted/Under Review |
| Health Point Ethics Committee |
Submittted/Under Review |
| Institutional Ethics Committee Bharati Vidyapeeth Deemed University |
Submittted/Under Review |
| Institutional Ethics Committee HCG Cancer Centre |
Approved |
| Institutional Ethics Committee, AKHMC, Nagpur |
Submittted/Under Review |
| KVT Speciality Hospital-IEC |
Submittted/Under Review |
| Medstar Speciality Hospital Ethics Committee |
Submittted/Under Review |
| PP Maniya Hospital Ethics Committee |
Approved |
| Zenith Institutional Ethics Committee |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C929||Myeloid leukemia, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Azacitidine 300 mg Film coated tablets |
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)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
28/04/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
02/05/2024 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="8"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
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. |