CTRI/2023/08/056807 [Registered on: 23/08/2023] Trial Registered Prospectively
Last Modified On:
15/11/2024
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
This is a drug concentration assessment study of Azacitidine 300 mg tablets in patients with Blood Cancer (Acute Myeloid Leukemia).
Scientific Title of Study
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.
2l3, W High Ct Rd, near Shankar Nagar, Square, Dharampcth, Nagpur,
Maharashtra 440010 Nagpur MAHARASHTRA
9823012851
drshriramkane@gmail.com
Dr Damodar Das
Gauhati Medical college and Hospital
Gauhati Medical college and Hospital
Dept of clinical hematology, 3rd floor Gauhati Medical college and Hospital, Bhangagarh , Guwahati - 781032 Assam India. Kamrup ASSAM
8638167301
dasdd18@gmail.com
Dr K S Senthilkumar
Harshamitra Super Speciality Cancer Hospital and Research Institute
Mathur Panchayat Road, Trichy-Madurai Highway, Nagamangalam, Trichy- 620012 Tiruchirappalli TAMIL NADU
9943408416
drkssk77@gmail.com
Dr Ramesh Uppada
HCG Cancer Centre
Room 2 (Ground floor) , Oncology departmentt, Plot no 10, survet no 13P, APIIC Health city, Chinagadili. Arilova, VisakhaPatnam-
530040. Andra Pradesh Visakhapatnam ANDHRA PRADESH
9494708778
drramesh.u@hcgel.com
Dr Nishad Dhakate
HCG NGHRI Cancer Centre
Dept. Of Haemato-Oncology. HCG NGHRI Cancer Centre ,50, 51 Mouja Bande Nawaz .’Nagar. Near Automotive Square. Kalamana Ring Read. Nagpur-
440026 Nagpur MAHARASHTRA
7042832629
drnishaddhakate@hcgel.com
Dr Shuvra Neel Baul
Health Point Hospital
Clinical research department, OPD building 1st Floor (Research Room) 21, Prannath Pandit St, Lansdown. Padamapukur, Kolkata, West
Bengal 700025 Kolkata WEST BENGAL
9062015351
shuvraneelb@gmail.com
Dr Sandip Abhaykumar Shah
Hemato Oncology Clinic
Clinical Research Room, Hemato Oncology Clinic Ahmedabad Pvt LTd, 1st Floor, Vedanta Insitute of Medical Science, Near Samved Hospital, Stadium Commerce College Road, Navrangpura, Ahmedabdad 380009 Ahmadabad GUJARAT
9824041170
sandip60@yahoo.com
Dr Manoj Toshniwal
Ishwar Institute of Health Care
Ishwar Heights, 1st floor, plot no 7, Gut no 6/1, beside Punjabi bhawan, Padegoan, Aurangabad-431002,
Maharashtra, India. Aurangabad MAHARASHTRA
9822314268
drmanojtoshniwal.iicr@gmail.com
Dr M Pandidurai
Meridian Hospital
Clinical Research Room, 49 D, Jawaharlal Nehru Road, 200 Feet Ring Road, Kolathur, Chennai- 600 099 Chennai TAMIL NADU
8248461542
pandi19@gmail.com
Dr P K Chaithanya
MNJ institute of oncology and regional cancer center
3rd floor, Clinical trial room No.11, Red Hills Hyderabad
Telangana - 500004 India Hyderabad TELANGANA
2nd Floor, Majithia
Apartments, Gods Gift
Premises, Co-op.
Society Ltd., Above Irla
Nursing Home, S.V
Road, Vile Parle (W),
Mumbai 400 056 Mumbai MAHARASHTRA
9167009042
ashjoshi44@mocindia.co.in
Dr Smitha Saldana
Nano Hospital
# 79 Sir M.Visveswaraya Road, Near Arekere Sai Baha Temple. Off Bannerghatta Road, Bengaluru-560076 Bangalore KARNATAKA
9480852106
saldanhasmitha@gmail.com
Dr Abhijit Subhashchandra Baheti
Noble Hospital Pvt. Ltd.,
Room No. 1,Clinical research
department Noble Annex 153, Magarpatta City Road,
Hadapsar Pune 411013, Maharashtra, India Pune MAHARASHTRA
9822426177
baheti.abhijit@gmail.com
Dr Faisal Rashid Guru
Sher-I-Kashmir Institute of Medical Sciences
Department of Medical
Oncology building, 1st floor, Room 103, State Cancer Institute, Soura,
Srinagar. Jammu &
Kashmir - 190011 Srinagar JAMMU & KASHMIR
9717017022
faisal_guru@yahoo.com
Dr Bafna Varun Ashok
Star Superspccility Hospital
1st floor, Clinical Research department, Rukmini Nagar. E Ward, Near LIC Ground , Kolhapur- 416005, Maharashtra. Kolhapur MAHARASHTRA
Ethics committee of Ishwar Institute of Health Care
Approved
HCG NCHRI CANCER CENTRE IEC
Approved
HEALTH POINT ETHICS COMMITTEE
Approved
IEC-SKIMS
Approved
Institutional Ethics Committee AMAN Hospital AND Research Centre
Approved
Institutional Ethics Committee Harshamitra Superspeciality Cancer Centre
Approved
Institutional Ethics Committee HCG Cancer Centre
Approved
Institutional Ethics Committee, GMCH- Dr. Damodar Das
Approved
Institutional Ethics Committee-Noble Hospital
Approved
Jasleen Hospital Ethics Committee
Approved
KVT Speciality Hospital - IEC - Dr. M Pandidurai
Approved
Medstar specialty Hospital Ethics committee
Approved
MNJIORCC Ethics committee
Approved
MohandaiOswal Cancer Treatment Research Foundation
Approved
Mumbai Oncocare Centre IEC
Approved
Om Sai Onco Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C950||Acute leukemia of unspecified celltype,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Azacitidine 300 mg film-coated tablet of Lotus Pharmaceuticals Co Ltd.
Azacitidine 300 mg film coated tablet, Route of administration : orally once daily in the morning. One day
Comparator Agent
ONUREGTM (azacitidine) film-coated tablets, 300mg of Bristol-Myers Squibb Pharma EEIG
ONUREGTM (azacitidine) film-coated tablets Route of administration : orally once daily in the morning. Two days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
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 system Parameters
Bone marrow function a) Hemoglobin ≥8.0 g/dL
b) Absolute neutrophil count ≥1000/uL
c) Platelet count ≥75,000/uL
Renal function Creatinine Clearance ≥ 30 mL/min (calculated based on Cockcroft-Gault formula)
Hepatic function Total 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 0-3.
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. Cessation of birth control after this point should be discussed with a responsible physician.
ExclusionCriteria
Details
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.
Note: Elimination half-life of the study drug should be taken in to consideration for inclusion of the patient in the 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.
11. 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
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.
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)
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events & to ensure the safety of the patients.
Day 1, Day 2, day 3, Day 4
Target Sample Size
Total Sample Size="60" Sample Size from India="60" Final Enrollment numbers achieved (Total)= "60" Final Enrollment numbers achieved (India)="60"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
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
üCheck in on Day 0 ( 11 hours prior to drug administration of Day 1)
üStudy 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.
üHospitalization 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.
üPK Sampling onDay 1 to Day 3 of the study.
üEnd 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.