CTRI/2023/09/057633 [Registered on: 14/09/2023] Trial Registered Prospectively
Last Modified On:
22/12/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Crossover Trial
Public Title of Study
Pharmacokinetic Study of Pazopanib in Advanced Renal Cell Carcinoma patients
Scientific Title of Study
A multi-center, open-label, balanced, randomized, two-treatment, two-period, two-sequence, two-way crossover, multiple-dose, steady-state bioequivalence study of Pazopanib HCl Tablets 200 mg (4 Tablets X 200 mg) of MSN Laboratories Private Limited, India compared with Votrient® Tablet 200mg (4 Tablets X 200 mg) of Novartis Pharmaceuticals Corporation, USA in Advanced renal cell carcinoma patients who are already receiving Pazopanib HCl tablets in standard therapy, and who are tolerating a stable dosing regimen of 800 mg/day under fasting conditions.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CSC-CT-021 Version 02 dated 11 Feb 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr K Babji
Designation
Principal Investigator
Affiliation
Clinsync Clinical Research Pvt. Ltd
Address
JSR Mall, Plot No. 7 to 18, Madinaguda Village, Serilingampally Mandal, Hyderabad, Ranga Reddy, Telangana- 500050
Hyderabad
TELANGANA
500050
India
Hyderabad TELANGANA 500050 India
Phone
8919041740
Fax
91-40-29887005
Email
babji.k@clinsynccro.com
Details of Contact Person Scientific Query
Name
Dr K Babji
Designation
Principal Investigator
Affiliation
Clinsync Clinical Research Pvt. Ltd
Address
JSR Mall, Plot No. 7 to 18, Madinaguda Village, Serilingampally Mandal, Hyderabad, Ranga Reddy, Telangana- 500050
Hyderabad
TELANGANA
500050
India
Hyderabad TELANGANA 500050 India
Phone
8919041740
Fax
91-40-29887005
Email
babji.k@clinsynccro.com
Details of Contact Person Public Query
Name
Suman Avula
Designation
Head Clinical Operations
Affiliation
Clinsync Clinical Research Pvt. Ltd
Address
JSR Mall, Plot No. 7 to 18, Madinaguda Village, Serilingampally Mandal, Hyderabad, Ranga Reddy, Telangana- 500050
Hyderabad
TELANGANA
500050
India
Department of Clinical Research,33-25-33, CH Venkatakrishnayya Street, Suryarao pet, Vijayawada-520002 Krishna ANDHRA PRADESH
9966030988
priyadarshini006@gmail.com
Dr Raj Nagarkar
HCG Manavata Cancer Centre
HCG Manavata Cancer Centre,
Behind Shivang Auto, Mumbai Naka,
Nashik 422002, Maharashtra, India
Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Vaibhav Amale
Horizon Multispeciality Hospital Sangli
Department of clinical research, 3rd Floor, 1592, 3rd Lane, Ganesh nagar Sangli, -416416 Maharshtra
Sangli
MAHARASHTRA Sangli MAHARASHTRA
8390913771
vai7444@gmail.com
Dr Minish Jain
Inamdar Multispecialty Hospital
Hospital Building ,Basement, Research Room, S.No. 15 Fatima nagar, Pune , Maharastra 411040
Pune
MAHARASHTRA Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr Asma Pathan
Indrayani Hospital and Cancer Institute
Department of clinical research, ground floor,shree Narsimha saraswati medical foundation, Alandi-Chakan Road, Alandi-Devachi, Pune, Maharashtra-412105, India.
Pune
MAHARASHTRA Pune MAHARASHTRA
8007167716
asmapathan124@gmail.com
Dr Koushik Chatterjee
Life Line Diagnostic Centre Cum Nursing Home
Clinical Research Department,Room No: 201,2nd floor,4A,Wood Street,Kolkata-700016, West Bengal,India.
Kolkata WEST BENGAL
9874357580
drkoushik.chatterjee@gmail.com
DrSatish Sonawane
Maccare Superspeciality Hospital Ahmednagar
Clinical research department, 4th floor, Behind Zopadi canteen,Opp St Monica D.ed College,Savedi,Ahmednagar-414003, Maharashtra
Ahmadnagar
MAHARASHTRA Ahmadnagar MAHARASHTRA
9730099999
satishujjwal@yahoo.com
Dr Tushar Mule
Marathwada Cancer Hospital & Research Institute
Clinical research department, Room no-404, 4th floor, Plot no. 02, Dyaneshwar nagar, In front of stadium, Garkheda, Aurangabad 431001, Maharashtra, India
Aurangabad MAHARASHTRA
9820403558
dr.tusharmchri@gmail.com
P K Chaithanya
MNJ Institute of Oncology & Regional Cancer Center
Clinical Trial room, room no 11, 3rd floor, Red Hills, hyderabad-500004, Telangana, India Hyderabad TELANGANA
8897199994
mnjiorccchaithanya@gmail.com
Dr Ashish Joshi
Mumbai Oncocare Centre, Mumbai
2nd Floor ,Majithia Aparatment, God’s gift Premises co-Op. Society Ltd., S.V. Road, Vile Parle (West)-400056, Mumbai, Maharashtra, India.
Mumbai
MAHARASHTRA Mumbai MAHARASHTRA
9920767626
ashjoshi44@mocindia.co.in
Dr Pritam Kalaskar
Mumbai Oncocare Centre, Thane
1st Floor, Blue Nile Building, Almeda Road, Next to Pinnacle Hospital, Charai Naka, Thane-400601, Maharashtra, India.
Thane
MAHARASHTRA Thane MAHARASHTRA
882800863
pritamkalaskarht@gmail.com
Dr Anil Kumar M R
Oncoville Cancer Hospital & Research Centre
Oncoville Cancer Hospital & Research Centre,
No 4, 80 ft rd, 7thBlock, Karnataka, India,
Banglore- 560072, Karnataka, India
Bangalore KARNATAKA
9739808502
dranil.onco@gmail.com
Dr Rakesh Neve
PDA’s Ayurvedic Rugnalaya and Sterling Multispeciality HospitalSterling Multispeciality Hospital
Department of clinical research,3rd Floor Sec. No. 27, Near Bhel Chowk, Nigdi, Pune-411044, Maharashtra, India.
Pune
MAHARASHTRA Pune MAHARASHTRA
9881143140
rakesh.neve@gmail.com
Dr Madhuchanda Kar
Peerless Hospitex Hospital & Research Centre Ltd
Department of Oncology,2nd Floor, 360, Panchasayar, Kolkata-700094, West Bengal, India.
Kolkata
WEST BENGAL Kolkata WEST BENGAL
Department of Urology, Ground floor,Uro-Science Centre,Ground Floor,Bikaner,-334003, Rajasthan, India.
Bikaner
RAJASTHAN Bikaner RAJASTHAN
9782300231
mcarya@yahoo.com
Dr Ashish Madhukarji Vaidya
Siddharth Gupta Memorial Cancer Hospital, A Unit of Acharya Vinoba Bhave Rural Hospital
Clinical Research Division,Siddharth Gupta Memorial Cancer Hospital, A unit of Acharya Vinoba Bhave Rural Hospital, Datta Meghe Institute of Higher Education and Research Sawangi (Meghe) Wardha-442004, Maharashtra. Wardha MAHARASHTRA
Institutional Ethics Committee BVDU Medical College and Hospital, Sangli
Approved
Institutional Ethics Committee Datta Meghe Institute of Higher Education and Research Sawangi (M)
Approved
Institutional Ethics Committee of Life Line Diagnostic Centre Cum Nursing Home
Approved
Institutional Ethics Committee Oncoville Cancer Hospital & Research Centre
Approved
Institutional Ethics Committee, RIMS, Ranchi
Approved
Manavata Clinical Research Institute
Approved
Mumbai Oncocare Centre IEC
Approved
Mumbai Oncocare Centre Institutional Ethics Committee,Thane
Approved
Narsimha Saraswati Medical Foundation Ethics Committee, lndrayani Hospital And Cancer Institute
Approved
Sai Urology Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C649||Malignant neoplasm of unspecifiedkidney, except renal pelvis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Pazopanib HCl Tablets 200 mg of MSN Laboratories Private Limited, India
Patients will be randomly assigned in a 1:1 ratio to receive either MSN Laboratories Private Limited, Indias Pazopanib 800 mg tablet (4×200 mg) or VOTRIENT® (pazopanib) 800 mg tablet (4×200 mg) once daily for 14 days in each period. On Day 15,patients will cross over to the other formulation as per randomization schedule for the next 14 days
Comparator Agent
Votrient® Tablet 200mg of Novartis Pharmaceuticals Corporation, USA
Patients will be randomly assigned in a 1:1 ratio to receive either VOTRIENT® (pazopanib) 800 mg tablet (4×200 mg) or MSN Laboratories Private Limited, Indias Pazopanib 800 mg tablet (4×200 mg) once daily for 14 days in each period. On Day 15,patients will cross over to the other formulation as per randomization schedule for the next 14 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
Patients should fulfil all inclusion and none of the Exclusion criteria for enrolment in the study.
1. Male or non-pregnant female patients between 18 - 75 years of age.
2. Patient willing to give written informed consent and comply with treatment and follow up.
3. Patient whose organ and immune system functions are normal or adequate as indicated by the laboratory values or considered by the Investigator/sub-Investigator to be of no clinical significanceâ€.
Hematologic:Absolute neutrophil count (ANC) ≥ 1.5 X 109/L Platelets ≥ 100 X 109/L Hemoglobin ≥ 9.0 g/dL Prothrombin Time (PT) ≤ 1.2 X ULN International Normalized Ratio (INR) ≤ 1.2 X ULN activated Partial Thromboplastin Time (aPTT) ≤ 1.2 X ULN,Hepatic:Total bilirubin ≤ 1.5 X ULN AST and ALT ≤ 2.0 X ULN,Renal;Serum creatinine ≤ 2 mg/dL Creatinine clearance ≥ 30 mL/min
4. Histopathological or Radiological diagnosis (Only PET Scan) of advanced RCC patient.
5. No significant medical comorbidities or inter current illnesses that could limit compliance with study medications or increase the risk of treatment-related toxicities.
6. Patients with confirmed advanced RCC who are on a stable dose (at least 28 days) of pazopanib tablets 800 mg once daily.
7. Patient, who in the opinion of the Investigator has a life expectancy greater than or equal to 3 months from the time of the first dose.
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2(Appendix 4).
9. No persistent toxicities from prior medications [Recovery to baseline or less than or equal to Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (or) higher and/or stable on supportive therapy at screening visit if any toxicities had occurred unless the toxicities were clinically insignificant].
10. Patient with cardiac ejection fraction within the normal range as measured by echocardiogram.
11. The patient must have a clinically acceptable 12-lead ECG at screening including QTc interval ≤ 480 msec.
12. Patient must have clinically acceptable results for all the screening parameters and investigations.
13. Able to swallow and retain orally administered medication.
14. Availability of patient for the entire study duration and willingness to adhere to protocol requirements as evidenced by written informed consent.
15. Female patient
a) of childbearing potential practicing an acceptable method of birth control such as sexual abstinence, (other than hormonal contraceptives) e.g. barrier method (diaphragm, condom, etc.); for the duration of the study as judged by the investigator(s)/study physician and agree to follow the same during treatment and for at least two weeks after the last dose or withdrawal/ discontinuation from the study. The patient agrees to accept the risk that pregnancy could still result despite using birth control devices. OR
b) Postmenopausal for at least the past 12 months. OR
c) Surgically sterile (bilateral tubal ligation/bilateral oophorectomy/hysterectomy has been performed on the patient).
16. Male patient must agree to practice an acceptable method of birth control such as sexual abstinence, a barrier method of contraception (i.e. condom) for the duration of the study as judged by the investigator(s)/study physician and agree to follow the same treatment and for at least two weeks after the last dose treatment or discontinuation /withdrawal from the study. The patient agrees to accept the risk that pregnancy in a female partner could still result despite using birth control devices.
ExclusionCriteria
Details
1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half lives of enrollment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
2. If patient’s current dose cannot be given using multiples of the dosage strength being studied
3. ECOG performance status 2
4. Pregnant or nursing (lactating) women
5. Hypokalemia, hypomagnesemia, long QT syndrome, or a history of cardiac disease.
6. Receiving any medications or substances that are strong inhibitors or inducers of the CYP450 enzyme.
7. Receiving any drugs known to prolong the QT interval within 4 weeks prior to study or during the study.
8. Unable to swallow and retain orally administered medication.
9. Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to beginning study treatment.
10. Any of the following cardiovascular conditions:
• history or presence of stable or unstable ischemic heart disease (IHD), myocardial infarction, myocarditis, or cardiomyopathy
• history of angina pectoris due to coronary spasm
• cardiac failure at time of Screening (Class II- IV, according to NYHA Classification) or any severe cardiac disease as determined by the investigator
• history of cardiac arrest
• history or presence of a clinically relevant impairment of cardiac conduction including sick sinus syndrome, or sino-atrial heart block, clinically significant AV block, bundle branch block or QTc 450 msec for males and 470 msec for females at Screening ECG
• history or presence of symptomatic arrhythmia or arrhythmia requiring treatment or being otherwise of clinical significance
• history of syncopes of suspected cardiac origin
11. Any of the following pulmonary conditions:
• pulmonary fibrosis or any severe respiratory disease
• tuberculosis, subjects receiving chronic (daily) therapies for asthma
• subjects with any other types of clinically significant bronchoconstrictive disease
12. Repeated and confirmed laboratory findings showing:
• known history of alcohol abuse, chronic liver or biliary disease
• total bilirubin greater than the upper limit of the normal range (ULN) unless in context of Gilbert’s syndrome
• conjugated bilirubin greater than the 1.5 x ULN
• alkaline phosphatase (AP) greater than 1.5 x ULN
• AST (SGOT), ALT (SGPT) greater than 2 x ULN
• platelets ≤ 100,000/µL
• Any signs of severe anemia.
• ANC 1500/mm3 (1500 / µL)
13. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drug, or which may jeopardize the subject in case of participation in the study.
14. Positive alcohol or drug abuse test at screening.
15. Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to randomization.
16. Significant illness within the two weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention during the study.
17. Current history of active systemic bacterial, viral or fungal infections
18. Diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests, respectively.
19. History of hypersensitivity to Pazopanib compound and/ or its class.
20. Presence or history of underlying metabolic, endocrine, hematologic, pulmonary, cardiac, blood, renal, hepatic, infectious, psychiatric or any medically unstable condition, as assessed by the primary treating physician which, in the opinion of the investigator, would compromise the subject and/or place the subject at unacceptable risk for participation in a study.
21. History of blood loss (approximately 1 U) 90 days prior to screening.
22. Any other condition or abnormal findings that, in the investigator’s judgment, might increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
23. Subject with a history of difficulty in donating blood or difficulty in accessibility of veins.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence of Pazopanib HCl Tablets 200 mg (4 Tablets X 200 mg) of MSN Laboratories Private Limited, India with Votrient® Tablet 200mg (4 Tablets X 200 mg) of Novartis Pharmaceuticals Corporation, USA, among Advanced renal cell carcinoma patients who are already receiving Pazopanib HCl tablets in standard therapy, & who are tolerating a stable dosing regimen of 800 mg/day under fasting conditions
A total of 19 blood samples (1 x 03 mL) will be collected from each patient in each period.
The pre-dose blood sample at 0.00 hr (1 x 03 mL) will be collected within 0.50 hr of scheduled dosing time on days 12, 13, & 14 in period I & 26, 27 & 28 in period II.
On days 14 (period I) and 28 (period II), blood samples will be collected at 0.50, 1.00, 1.50, 2.00, 2.50, 3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 08.00, 10.00, 12.00, 16.00 and 24.00 hours post dose.
Secondary Outcome
Outcome
TimePoints
To monitor the safety & tolerability of Pazopanib HCl Tablets 200 mg (4 Tablets X 200 mg) among Advanced renal cell carcinoma patients who are already receiving Pazopanib HCl tablets in standard therapy, and who are tolerating a stable dosing regimen of 800 mg/day under fasting conditions
28 days
Target Sample Size
Total Sample Size="52" Sample Size from India="52" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
A multicentre, randomized, two way crossover bioequivalence study, comparing Pazopanib hydrochloride in Test and Reference drugs, in patients with Advanced Renal Cell Carcinoma.