CTRI/2022/04/042340 [Registered on: 29/04/2022] Trial Registered Prospectively
Last Modified On:
17/07/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
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
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) Modification(s)
Name
Dr K Babji
Designation
Principal Investigator
Affiliation
M/s. 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
Phone
8919041740
Fax
91-40-29887005
Email
babji.k@clinsynccro.com
Details of Contact Person Scientific Query
Name
Dr Sanjay V Vaze
Designation
Principal Investigator
Affiliation
M/s. 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
Phone
91-9322344635
Fax
91-40-30438667
Email
sanjayvishnu.v@clinsynccro.com
Details of Contact Person Public Query
Name
Dr Neeta Nargundkar
Designation
Managing Director
Affiliation
Biosphere Clinical Research Pvt Ltd
Address
Office No. 02, 03 & 04, 2nd Floor Highland Corporate Center,
Kapurbawdi Junction, Thane west
Thane
MAHARASHTRA
Department of Urology,Room no. 31,Baba Kharag Singh Marg, New Delhi-110001, India. New Delhi DELHI
9810005182
drsoodr@gmail.com
Dr Ravindra Nandhana
Great Eastern Medical School and Hospital Srikakulam
Department of Medical Onclology, D.No 3-351,Ragolu Srikakulam
Andhra Pradesh - 532484 India
Srikakulam ANDHRA PRADESH
7396167309
drravindranandhanaresearch@gmail.com
Dr Vaibhav Amale
Horizon Multispeciality Hospital Sangli
Department of clinical research, 3rd Floor, 1592, 3rd Lane, Ganesh nagar Sangli, -416416 Maharshtra 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
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
8007167716
asmapathan124@gmail.com
DrSatish Sonawane
Maccare Superspeciality Hospital Ahmednagar
Behind Zopadi canteen,Opp St Monica D.ed College,Savedi,Ahmednagar-414003, Maharashtra Ahmadnagar MAHARASHTRA
9730099999
satishujjwal@yahoo.com
Dr Tushar Mule
Marathwada Cancer Hospital & Research Institute
Plot no. 02, Dyaneshwar nagar, In front of stadium, Garkheda, Aurangabad 431001, Maharashtra, India Aurangabad MAHARASHTRA
9820403558
dr.tusharmchri@gmail.com
Dr Balaji Shewalkar
Marathwada Regional Cancer Center & Research Institute
Dept of Radiotherapy and Oncology,Near Jama Masjid, Kil-E-Ark, Aurangabad-431001, Maharashtra, India. Aurangabad MAHARASHTRA
9850632639
bkrish1970@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
9920767626
ashjoshi44@mocindia.co.in
Dr Chandrakant Pethe
Mumbai Oncocare Centre, Nashik
Plot No. 4 & 5, S. No. 277/1/3, Near Indrayani Lawns, Aurangabad Road, Nashik-422003, Maharashtra, India. Nashik MAHARASHTRA
8888736446
drcvpethe@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
882800863
pritamkalaskarht@gmail.com
Dr Anupam Datta
Netaji Subhash Chandra Bose Cancer Hospital
Department of Clinical Research,R.No 402,3081, Nayabad, New Garia, Kolkata-700094, West Bengal, India. Kolkata WEST BENGAL
91-9163067435
dranupamdatta@gmail.com
Dr B Ravi Shankar
Omega Hospitals
Plot No. 4, Health city, China Gadhili, Hanumanthavaka, Visakhapattanam-530040, India. Visakhapatnam ANDHRA PRADESH
9849123256
ravi_bellala@yahoo.co.in
Dr Siddhesh Tryambake
Oncolife Cancer Centre
Clinical Research department,6th Floor, Survey No. 252, Near Pune-Banglore Highway, Shendre, Satara-415519, Maharashtra, India Satara MAHARASHTRA
8626042701
dr.srtryambake@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
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
Mumbai Oncocare Centre Institutional Ethics Committee,Mumbai
Approved
Mumbai Oncocare Centre Institutional Ethics Committee,Thane
Approved
Narsimha Saraswati Medical Foundation Ethics Committee, Indrayani Hospital and Cancer Institute
Approved
Peerless Hospitex Hospital & Research Center Ltd. - Clinical Research Ethics Committee
Approved
Sai Urology Hospital Ethics Committee Aurangabad
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. Pregnant and lactating female.
2. Patient receiving any medications or substances that are strong inhibitors or inducers of the CYP450 enzyme.
3. Patient having any history or receiving any drugs known to prolong the QT interval within 4 weeks before the study or using Bazett’s Formula.
4. Patient with risk factors for prolonged QTc interval and Torsades de Pointes..
5. Patient participated in any study which involves blood loss in the last 90 days and/or donated blood (1 unit or 350 ml) within 90 days prior to dosing in the study and/ or history of difficulty with donating blood.
6. Patient with brain metastases as confirmed by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI).
7. Patient with history of pre-existing thyroid abnormality that cannot be maintained in the normal range with medication.
8. Patient with clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
- Active peptic ulcer disease.
- Known intraluminal metastatic lesion/s with the risk of bleeding.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days before study treatment.
- Malabsorption syndrome
- Major resection of the stomach or small bowel.
9. Any other significant medical comorbidities or intercurrent illnesses or infection which may have an impact on patient safety and do not permit the dosing of Pazopanib HCl as determined by the Investigator.
10. Patient with uncontrolled hypertension while receiving appropriate medication (systolic blood pressure ≥ 150 mmHg and diastolic blood pressure > 90 mmHg).
11. Abnormal electrolytes (Sodium, Potassium, Calcium & Magnesium) or patient with long QT syndrome.
12. Presence of proteinuria.
13. History of any one of the following cardiac conditions within the past 6 months;
- Cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, coronary artery by-pass graft surgery, class III or IV congestive heart failure as per NYHA, serious cardiac arrhythmias, cerebrovascular accident, stroke (including transient ischemic attack), pulmonary embolism or untreated deep venous thrombosis.
14. Haemoptysis within 6 weeks of screening.
15. Evidence of bleeding diathesis or coagulopathy.
16. Anticoagulant treatment with curative intent.
17. Alcohol dependence, alcohol abuse, or drug abuse, or addiction with any recreational drug within the past year.
18. Patient who have consumed grapefruit, citrus fruits, and its products for 48 hours before first dosing.
19. Patient who have consumed any xanthine-containing items (i.e. tea, coffee, cola drinks, or chocolate/coca, etc.) for 48 hours before first dosing.
20. Allergy or significant history of hypersensitivity or idiosyncratic reactions to study drug product or its excipients etc.
21. History of difficulty in swallowing.
22. Clinically assessed as having inadequate venous access for PK sampling.
23. Patient deemed uncooperative or non-compliant.
24. Patient who have shown positive results in urine alcohol test and/or urine drug screening test.
25. Significant abnormal 12 lead ECG, Chest X-ray, and 2D-Echocardiography finding.
26. A positive result of HIV, HCV, RPR, and HbsAg
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, and 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, and 14 in period I and 26, 27 and 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 and 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
This study is a 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.
The Primary objective is 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, and who are tolerating a stable dosing regimen of 800 mg/day under fasting conditions.
The Secondary objective is to monitor the safety and 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