CTRI

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CTRI Number

CTRI/2024/11/076347 [Registered on: 06/11/2024] Trial Registered Prospectively

Last Modified On:

26/12/2024

Post Graduate Thesis

Type of Trial

Interventional

Type of Study

Drug

Study Design

Randomized, Crossover Trial

Public Title of Study

A study of Azacitidine 300 mg tablets in adult patients with Acute Myeloid Leukemia (AML) .

Scientific Title of Study

A randomized, open label, balanced, multicenter, two-treatment, four-period, two-sequence, single-dose, full-replicate, cross-over bioequivalence study of Azacitidine 300 mg film-coated tablets compared to ONUREG 300 mg film-coated tablets in adult patients with Acute Myeloid Leukaemia (AML) under fasting conditions.

Trial Acronym

Nil

Secondary IDs if Any

Secondary ID	Identifier
24-VIN-0129, V01 dated 17 Jun 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 GUJARAT 380015 India
Phone	8308843660
Fax
Email	rakesh.patel@veedacr.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 GUJARAT 380015 India
Phone	9687306158
Fax
Email	Ravi.A1950@veedacr.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 GUJARAT 380015 India
Phone	9687306158
Fax
Email	Ravi.A1950@veedacr.com

Source of Monetary or Material Support

Synthon B.V. Microweg 22 6545 CM Nijmegen The Netherlands

Primary Sponsor

Name	Synthon B.V.
Address	Microweg 22 6545 CM Nijmegen The Netherlands,
Type of Sponsor	Pharmaceutical industry-Global

Details of Secondary Sponsor

Name	Address
Veeda Clinical Research Ltd	Shivalik Plaza, Near I.I.M., Ambawadi Ahmedabad â€“ 380 015, India

Countries of Recruitment

India

Sites of Study

No of Sites = 12
Name of Principal Investigator	Name of Site	Site Address	Phone/Fax/Email
Dr Priyanka Verma	Apollo Specialty Hospital Pvt. Ltd.	14/138, Chunni Ganj, Kanpur Kanpur Nagar Uttar Pradesh - 208001 India Kanpur Nagar UTTAR PRADESH	9953562596 dr.priyankverma21@gmail.com
Dr Shriram Bhagwan Kane	Asian Kidney Hospital & Medical Centre	213, W High Ct Rd, Near Shankar Nagar Square, Dharmapeth Nagpur 440010, Nagpur MAHARASHTRA	9823012851 shriramkane@gmail.com
Dr Varun Bafna	Dr. Bafna SuperSpeciality Clinic & Star HospitalÂ	clinical research department, 2nd floor, Rukmani Nagar, E Ward Near LIC Ground Kolhapur - 416005 Kolhapur MAHARASHTRA	9066565353 drvarunbafna6@gmail.com
Dr Ramesh Upada	HCG Cancer Center	Room 2 (Ground floor), Oncology Department, Plot no 10, Survey no 13P, APIIC Health City, Chinagadili. Arilova, Visakhapatnam- 530040. Visakhapatnam ANDHRA PRADESH	9494708778 drramesh.u@hcgel.com
Dr Amarnadh Polisetty	HCG City Cancer Centre	33-25-33, CH Venkata Krishnayya Street Suryarao pet Vijaywada - 520002 Andhra Pradesh India. Krishna ANDHRA PRADESH	9611165090 amarnadhpolisetty@gmail.com
Dr Raj Nagarkar	HCG Manavta cancer center	Department of Clinical Research, HCG Manavta cancer center, Behind Shivang Auto Mumbai Naka Nashik, 422002 Nashik MAHARASHTRA	9823061929 drraj@manavatacancercentre.com
Dr Shuvra neel baul	Health Point Hospital	21, Prannath Pandit St. Lansdown, Paddapukur, Kolkata, 700025 Kolkata WEST BENGAL	9062015351 dr.shurva.n.baul@gmail.com
Dr Abhijit Baheti	Indrani Hospital and cancer institute	Clinical research room, Indrani Hospital and cancer institute, Alandi Chankan Road Alandi, Devachi, Charholi Budruk, Pune 412105 Pune MAHARASHTRA	9822426177 baheti.abhijit@gmail.com
Dr Manoj Toshniwal	Jeevan Amrut Hospital	Parijat nagar, Near Gokul Sweets N-4 , CIDCO , Chhatrapati Sambbhaji Nagar - 431007 MH INDIA Aurangabad MAHARASHTRA	9225300842 dr.manojtwal@gmail.com
Dr P Krishna Chaithanya	MNJ Cancer HospitalÂ	Room No 36 (Ground Floor) OPD Block,3ed Floor, Clinical Trial Room. 11. Medical Oncology Department, Redhills Road, Redhills, Lakadikapul, beside Niloufer Hospital, Telangana 500004 Hyderabad TELANGANA	8897199994 chaitanyakrishna.medonc@gmail.com
Dr Smitha Saldanha	Nano Hospital	79, Sir, M Visveswaraya Road Near Arekere Sai Baba Temple Off Bannerghatta Road Bangaluru -560076 Bangalore KARNATAKA	9480852106 saldanhasmitha@gmail.com
Dr Riya Balikar	Wockhardt cancer Institute	27, Corporation colony, North Ambazari Road Nagpur 440033 India Nagpur MAHARASHTRA	8334988584 riabalikar86@gmail.com

Details of Ethics Committee
Modification(s)

No of Ethics Committees= 12
Name of Committee	Approval Status
Apollo Specialty Hospitals Kanpur EC	Approved
ETHICS COMMITTEE WOCKHARDTHOSPTIALS LTD NAGPUR	Approved
HEALTH POINT ETHICS COMMITTEE	Approved
Institutional Ethics Committee HCG Cancer Centre	Approved
Institutional Ethics Committee HCG CURIE CITY CANCER CENTRE	Approved
Institutional Ethics Committee,AKHMC,Nagpur	Approved
ManavataClinicalResearchInstitute Ethics Committee	Approved
Medstar speciality Hospital Ethics Committee	Approved
MNJIORCC Ethics Committee	Approved
Narsimha Saraswati Medical Foundation Indrayani Hospital And Cancer Institute	Approved
Oriion Citicare Hospital Institute Ethics committee (OCH IEC)	Approved
Zenith Institutional Ethics committee	Approved

Regulatory Clearance Status from DCGI

Status

Approved/Obtained

Health Condition / Problems Studied

Health Type	Condition
Patients	(1) ICD-10 Condition: C926\|\|Acute myeloid leukemia with 11q23-abnormality,

Intervention / Comparator Agent

Type	Name	Details
Intervention	Azacitidine 300 mg film-coated tablets	Dose Formulation: Tablet,Unit Dose Strength(s):300 mg Dosage Level(s) 1 tablet of 300 mg orally in each period. Route of Administration: Oral Duration of Dose: Each participant will receive study intervention on Day 1, Day 2, Day 3 and Day 4 as per the randomization schedule.
Comparator Agent	ONUREG 300 mg film-coated tablets	Dose Formulation: Tablet,Unit Dose Strength(s):300 mg Dosage Level(s) 1 tablet of 300 mg orally in each period. Route of Administration: Oral Duration of Dose: Each participant will receive study intervention on Day 1, Day 2, Day 3 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. Able to give written informed consent for participation in the trial. 2. 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. 3. Patients meeting either one of the following criteria: â€¢ Patients that will be initiating treatment with Azacitidine 300 mg tablets as per the independent clinical judgement of the investigator. Or â€¢ Patients that are already receiving a stable dose of 300 mg Azacitidine 4. Patients with a history of treated brain metastases should be clinically stable for more than and equal to 4 weeks prior to signing the informed consent. Glucocorticoid therapy for central nervous system -CNS edema is permitted if the dose is less than or equal to 20 mg of prednisolone or equivalent . 5. Patients who are not eligible for or choose not to proceed to, hematopoietic stem cell transplantation -HSCT 6. Patients having a life expectancy of more than 3 months. 7. Adequate organ and bone marrow function based upon the following laboratory criteria at the time of eligibility assessment Hemoglobin more than and equal to 8.0 g/dL Absolute neutrophil count more than and equal to 1000/uL Platelet count more than and equal to 75,000/uL Creatinine Clearance more than and equal to 30 mL/min -calculated based on Cockcroft-Gault formula Total Bilirubin ï‚£ 1.5 times ULN SGOT - AST 2.5 times ULN SGPT - ALT 2.5 times ULN 8. Eastern Cooperative Oncology Group -ECOG performance status of 0-2 both inclusive. 9. 12-lead ECG with no clinically significant findings at screening as determined by the Investigator. 10. 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 administration. Cessation of birth control after this point should be discussed with a responsible physician. 11. In case of male patients: The patient must agree to use an effective method of contraception for at least 4 weeks prior to first study dose administration up to at least 3 months after the last dose of study drug administration. 12. Patients that are willing to comply with the study procedures in the opinion of Investigator.

ExclusionCriteria

Details

Patients who meet any of the following exclusion criteria at screening will not be enrolled in the study:
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, VDRL or RPR -for syphilis, Hepatitis B surface antigen or Hepatitis C antibody at screening.
3. Have ongoing clinically significant adverse event-s due to prior treatments administered, as determined by the investigator.
4. Had chemotherapy or radiotherapy within 4 weeks prior to the first day of Investigational Medicinal Product -IMP administration.
5. History of inflammatory bowel disease -e.g. Crohn s 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.
6. Patients with severe renal impairment.
7. Patients with severe hepatic impairment
8. 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.
9. In the opinion of the Investigator, the patient will not be compliant with the requirements of the study procedures.
10. 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.
Note: Elimination half-life of the study drug should be taken in to consideration for inclusion of the patient in the study.
11. History of difficulty in accessibility of veins.
12. Patient positive on Breath alcohol analyzer test at the time of screening and Check in Day 0.
13. Positive for drugs of abuse at the time of screening and Check in Day 0.
14. 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.
15. Patients with psychiatric illness social situations that would limit compliance with study requirements.
16. 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 s opinion, would contraindicate, or interfere with absorption of the study drug or jeopardize the safety of the patient.
17. Patients with impaired ability to swallow and retain oral medication.
18. Patients with uncontrolled systemic fungal, bacterial, or viral infection patients

Method of Generating Random Sequence

Stratified block randomization

Method of Concealment

Centralized

Blinding/Masking

Open Label

Primary Outcome

Outcome	TimePoints
To establish bioequivalence between Azacitidine 300 mg tablets (Test) and ONUREG 300 mg film-coated tablets (Reference) in adult patients with acute myeloid leukaemia (AML).	Day 1 - Period I, Day 2- Period II, Day 3 - Period III and Day 4 - Period IV: (full replicate BE study, each period is for 1 day)

Secondary Outcome

Outcome	TimePoints
To monitor the adverse events and to ensure the safety of the patients	Day 1 - Period I, Day 2- Period II, Day 3 - Period III and Day 4 - Period IV: (full replicate BE study, each period is for 1 day)

Target Sample Size

Total Sample Size="60"
Sample Size from India="60"
Final Enrollment numbers achieved (Total)= "60"
Final Enrollment numbers achieved (India)="60"

Phase of Trial

N/A

Date of First Enrollment (India)

20/11/2024

Date of Study Completion (India)

24/06/2025

Date of First Enrollment (Global)

Date Missing

Date of Study Completion (Global)

Date Missing

Estimated Duration of Trial

Years="1"
Months="0"
Days="0"

Recruitment Status of Trial (Global)

Not Applicable

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 a full replicate bioequivalence study between test and reference product in patients diagnosed with acute myeloid leukaemia (AML) (from multiple sites in India)

Patients will be randomly allocated to a treatment sequence of TRTR or RTRT.

The study consists of a screening period of 10 days and four treatment periods of 1 day each in the same treatment cycle; Period I on Day 1, Period II on Day 2], Period III on Day 3, and Period IV on Day 4.

Total duration of study will be 14 days (approximately) consists of a screening period of 10 days prior to first study drug administration wherein:

Ã¼ Check in on Day 0 (12 hours prior to drug administration of Day 1)

Ã¼ Study drug administration on Day 1 (period-I), Day 2 (period-II), Day 3 (period-III) and Day 4 (Period-IV)

Ã¼ Hospitalization on Day 0 (Check-in) to Day 4 (Check-out) in the study. For patient convenience, check-out may be done on Day 5 at the discretion of Investigator.

Ã¼ PK Sampling on Day 1 to Day 4 of the study.

Ã¼ End of the study after last PK sample collection on Day 4.